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| CAKUT v1.175 | ROBO1 | Arina Puzriakova Phenotypes for gene: ROBO1 were changed from unilateral kidney agenesis; bilateral kidney agenesis; vesicoureteral junction obstruction; vesicoureteral reflux; posterior urethral valve; genital malformation; increased kidney echogenicity to Neurooculorenal syndrome, OMIM:620305 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.174 | ROBO1 |
Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Laura Claus (UMC). Rating Green as there is enough evidence to support the gene-disease association. Included on the R27 Paediatric disorders GMS panel via inclusion on the R29 Intellectual disability panel. Biallelic variants in the ROBO1 gene are associated with neurooculorenal syndrome (OMIM:620305). Clinical manifestations are generally highly variable and involve several organ systems which may be include a syndromic form of congenital anomalies of the kidney and urinary tract (CAKUT) (PMID: 35227688) |
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| CAKUT v1.173 | COX10 | Arina Puzriakova Phenotypes for gene: COX10 were changed from Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due tocytochrome c oxidase deficiency to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due tocytochrome c oxidase deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.169 | ZMYM2 | Sarah Leigh Phenotypes for gene: ZMYM2 were changed from CAKUT; Abnormality of the urinary system; Global developmental delay; Intellectual disability; Microcephaly; Abnormality of the cardiovascular system; Autism; Seizures; Abnormality of the head or neck; Abnormality of the nail; Small hand; Short foot; Clinodactyly to Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, OMIM:619522 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.165 | TMEM260 | Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least eight variants have been reported in at least six unrelated cases. The variants included: one multi-exon deletion resulting in a frameshift, two smaller frameshifting deletions, two nonsense, one splicing change and two missense changes, one of which was shown by cDNA sequencing to result in skipping of exon 3 (PMID 34612517).; to: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least eight variants have been reported in at least six unrelated cases. The variants included: one multi-exon deletion resulting in a frameshift, two smaller frameshifting deletions, two nonsense, one splicing change and two missense changes, one of which was shown by cDNA sequencing to result in skipping of exon 3 (PMID 34612517). Renal features were seen in patients as follows: elevated creatinine levels (6/12), horse-shoe kidneys (1/12) and renal cysts (1/12)(PMID 34612517). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.165 | TMEM260 |
Sarah Leigh gene: TMEM260 was added gene: TMEM260 was added to CAKUT. Sources: Expert Review Amber,PAGE DD-Gene2Phenotype Q4_21_rating tags were added to gene: TMEM260. Mode of inheritance for gene: TMEM260 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMEM260 were set to 28318500; 34612517 Phenotypes for gene: TMEM260 were set to Structural heart defects and renal anomalies syndrome, OMIM:617478; Structural heart defects and renal anomalies syndrome, MONDO:0044321 |
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| CAKUT v1.163 | WBP11 | Ivone Leong Phenotypes for gene: WBP11 were changed from malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems to Vertebral, cardiac, tracheoesophageal, renal, and limb defects, OMIM:619227 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.161 | PLVAP |
Ivone Leong gene: PLVAP was added gene: PLVAP was added to CAKUT. Sources: Literature Mode of inheritance for gene: PLVAP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLVAP were set to 29875123; 29661969; 26207260; 31215290 Phenotypes for gene: PLVAP were set to Diarrhoea 10, protein-losing enteropathy type, OMIM:618183 Review for gene: PLVAP was set to GREEN Added comment: This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. It is currently Amber with a recommendation to promote to Green on the Intestinal failure panel (Version 1.36) with the following reviews: "Diarrhoea-10 is a protein-losing enteropathy characterized by intractable secretory diarrhoea and massive protein loss due to leaky fenestrated capillaries. Features include early-onset anasarca, severe hypoalbuminemia, hypogammaglobulinemia, and hypertriglyceridemia, as well as electrolyte abnormalities. Some patients exhibit facial dysmorphism and cardiac and renal anomalies. Intrafamilial variability has been observed, and the disease can be severe, with death occurring in infancy in some patients. Four unrelated families reported. Sources: Expert Review Zornitza Stark (Australian Genomics), 5 Jan 2021" "Comment on publications: PMID: 26207260. Patient is of Afgan descent born to consanguineous parents. Presented at 8 days of life with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures. Further examination shows patient had bilateral colobomas, undescended testes, mildly dysplastic kidneys bilaterally, low-set ears, and micrognathia. PMID: 29875123. 2 patients (first cousins) from a Muslim Arab consanguineous kindred presented with anasarca, severe hypoalbuminaemia and hypogammaglobinaemia. PMID: 29661969. Patient is of Turkish descent born to consanguineous parents. Presented with severe haematochezia and moderate anasarca. Other findings: dysmorphism, metabolic acidosis, electrolyte deficiencies, elevated GGT, choroid plexus cysts, iris cysts, ASD, VSD, dilated megaureter with dilated renal pelvis, venous thrombosis. PMID: 31215290. Patient born to consanguineous parents. As well as intestinal phenotypes, she also had dysmorphic features, renal and cardiac phenotypes. Ivone Leong (Genomics England Curator), 12 Apr 2021" After discussion with the Geomics England Clinical Team it was decided that this gene should also be on this panel. Sources: Literature |
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| CAKUT v1.160 | WBP11 | Eleanor Williams Added comment: Comment on list classification: Added to the panel at the suggestion of Genomics England clinicians. Promoting from red to green based on 4 unrelated cases with a renal phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.159 | WBP11 |
Eleanor Williams changed review comment from: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies. Sources: Literature; to: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies. A renal phenotype was seen in 5/13 patients from 4 families. Sources: Literature |
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| CAKUT v1.159 | WBP11 |
Eleanor Williams gene: WBP11 was added gene: WBP11 was added to CAKUT. Sources: Literature Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: WBP11 were set to 33276377 Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems Review for gene: WBP11 was set to GREEN Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies. Sources: Literature |
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| CAKUT v1.156 | HS2ST1 |
Ivone Leong gene: HS2ST1 was added gene: HS2ST1 was added to CAKUT. Sources: Literature watchlist tags were added to gene: HS2ST1. Mode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HS2ST1 were set to 33159882 Phenotypes for gene: HS2ST1 were set to Intellectual disability; dysmorphic features; congenital anomalies Review for gene: HS2ST1 was set to AMBER Added comment: This gene is not associated with a relevant phenotype in OMIM or Gene2Phenotype. Only 2 of 3 unrelated families with affected individuals described in PMID: 33159882 were reported to have ID. The affected individuals in the third family could not be assessed for ID. Other features affected individuals had were muscular hypotonia, hypoplasia/agenesis of corpus callosum, skeletal abnormalities, uni/bilateral renal agenesis (2/3) and craniofacial dysmorphism. This gene has been given an Amber rating. Sources: Literature |
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| CAKUT v1.154 | ZMYM2 |
Ivone Leong gene: ZMYM2 was added gene: ZMYM2 was added to CAKUT. Sources: Expert Review Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ZMYM2 were set to 32891193 Phenotypes for gene: ZMYM2 were set to CAKUT; Abnormality of the urinary system; Global developmental delay; Intellectual disability; Microcephaly; Abnormality of the cardiovascular system; Autism; Seizures; Abnormality of the head or neck; Abnormality of the nail; Small hand; Short foot; Clinodactyly Review for gene: ZMYM2 was set to GREEN Added comment: Review by Konstantinos Varvagiannis on the Intellectual disability panel: "Heterozygous pathogenic (pLoF) ZMYM2 variants have been reported in individuals with syndromic presentation including CAKUT (in several cases) and variable neurological manifestations among extra-renal features. DD and ID were reported in some of the families described to date as summarized below. You might consider inclusion with green/amber rating in the ID panel and green in the panel for CAKUT. -- Connaughton et al (2020 - PMID: 32891193) report on 19 individuals (from 15 unrelated families) with heterozygous pathogenic ZMYM2 variants. [Article not reviewed in detail]. Affected individuals from 7 families presented with CAKUT while all of them displayed extra-renal features. Neurological manifestations were reported in 16 individuals from 14 families (data not available for 1 fam), among others hypotonia (3/14 fam), speech delay (4/14 fam), global DD (9/14 fam), ID (4/14 fam), microcephaly (4/14 fam). ASD was reported in 4 fam (4 indiv). Seizures were reported in 2 fam (2 indiv). Variable other features included cardiac defects, facial dysmorphisms, small hands and feet with dys-/hypo-plastic nails and clinodactyly. 14 pLoF variants were identified, in most cases as de novo events (8 fam). In 2 families the variant was inherited from an affected parent. Germline mosaicism occurred in 1 family. The human disease features were recapitulated in a X. tropicalis morpholino knockdown, with expression of truncating variants failing to rescue renal and craniofacial defects. Heterozygous Zmym2-deficient mice also recapitulated the features of CAKUT. ZMYM2 (previously ZNF198) encodes a nuclear zinc finger protein localizing to the nucleus (and PML nuclear body). It has previously been identified as transcriptional corepressor interacting with nuclear receptors and the LSD1-CoREST-HDAC1 complex. It has also been shown to interact with FOXP transcription factors. The authors provide evidence for loss of interaction of the truncated ZMYM2 with FOXP1 (mutations in the latter having recently been reported in syndromic CAKUT). Sources: Literature Created: 19 Sep 2020, 1:07 a.m." Based on the expert review and evidence, there is enough evidence to support a gene-disease association. Therefore, this gene has been given a Green rating. Sources: Expert Review |
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| CAKUT v1.152 | DACT1 | Eleanor Williams changed review comment from: Conference presentation/abstract - C14.2 - Heterozygous DACT1 mutations in patients with renal anomalies and features of Townes-Brocks syndrome Helge Martens - WES in a patient with renal anomalies, i.e. left-sided agenesis and right-sided duplex, who also had extrarenal abnormalities, e.g. anorectal and sacral malformation, They found a rare heterozygous missense variant in DACT1 gene. The variant was inherited from an unaffected mother. Then looked in further patients and found 7 maternally inherited, heterozygous, likely pathogenic DACT1 missense variants in 8 of 209 families. Appears to be reduced penetrance. Functional assays found Dact1 expression in different organs including anal canal and kidney, whereby renal expression was confined to the mesenchyme of ureter, kidney capsule, cortical and medullary stroma in mouse embryos. CRISPR/Cas9-derived Dact1-deficient murine inner medullary collecting duct cells showed impaired tubule formation. No publication relating to this data is found in PubMed.; to: ESHG 2020 Conference presentation/abstract - C14.2 - Heterozygous DACT1 mutations in patients with renal anomalies and features of Townes-Brocks syndrome Helge Martens - WES in a patient with renal anomalies, i.e. left-sided agenesis and right-sided duplex, who also had extrarenal abnormalities, e.g. anorectal and sacral malformation, They found a rare heterozygous missense variant in DACT1 gene. The variant was inherited from an unaffected mother. Then looked in further patients and found 7 maternally inherited, heterozygous, likely pathogenic DACT1 missense variants in 8 of 209 families. Appears to be reduced penetrance. Functional assays found Dact1 expression in different organs including anal canal and kidney, whereby renal expression was confined to the mesenchyme of ureter, kidney capsule, cortical and medullary stroma in mouse embryos. CRISPR/Cas9-derived Dact1-deficient murine inner medullary collecting duct cells showed impaired tubule formation. No publication relating to this data is found in PubMed. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.152 | FOXD2 |
Eleanor Williams gene: FOXD2 was added gene: FOXD2 was added to CAKUT. Sources: Other Mode of inheritance for gene: FOXD2 was set to BIALLELIC, autosomal or pseudoautosomal Added comment: Conference presentation/abstract ESGH 2020 - Implication of FOXD2 in autosomal recessive syndromic CAKUT Korbinian M. Riedhammer Report index patient with CAKUT with a homozygous frameshift variant in FOXD2 NM_004474.3:c.789dup, p.(Gly264Argfs*228). The patient presented with bilateral hypoplastic kidneys, facial dysmorphism, developmental delay. Another affected family member was found to have the same variant. FOXD2 is a transcription factor with strong expression in the developing kidney. Foxd2-/- mice can show a CAKUT phenotype. No publications in PubMed relating to this data are currently found. Sources: Other |
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| CAKUT v1.151 | RPGRIP1L | Sarah Leigh changed review comment from: Comment on list classification: Rating changed from green to red, as the phenotypic features associated with RPGRIP1L variants are ciliopathies. It is green on Renal ciliopathies (https://panelapp.genomicsengland.co.uk/panels/725/gene/RPGRIP1L/) and Rare multisystem ciliopathy disorders (https://panelapp.genomicsengland.co.uk/panels/150/gene/RPGRIP1L/) panels.; to: Comment on list classification: Rating changed from green to red, as the phenotypic features associated with RPGRIP1L variants are ciliopathies and therefore not appropriate for the CAKUT panel. It is green on Renal ciliopathies (https://panelapp.genomicsengland.co.uk/panels/725/gene/RPGRIP1L/) and Rare multisystem ciliopathy disorders (https://panelapp.genomicsengland.co.uk/panels/150/gene/RPGRIP1L/) panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.151 | RRM2B | Sarah Leigh Added comment: Comment on list classification: Rating changed from green to red, as the phenotypic features associated with RRM2B variants are metabolic renal disease / renal tubulopathy. RRM2B is green on Mitochondrial disorders (https://panelapp.genomicsengland.co.uk/panels/112/gene/RRM2B/) and Inborn errors of metabolism (https://panelapp.genomicsengland.co.uk/panels/467/gene/RRM2B/) panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.148 | NIPBL | Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 13 variants reported, however, there seems to be little evidence of renal involvement.; to: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 13 variants reported. PMID 8291540 presents extensive evidence for renal involvement in 61 Cornelia de Lange syndrome 1 cases; including structural anomalies of the kidney system in 25 (41%): absent or poor corticomedullary differentiation (8 cases), pelvic dilation (6 cases), vesicoureteral reflux (5 cases), small kidney (3 cases), isolated renal cyst (3 cases), renal ectopia (2 cases), renal function reduced (9 cases). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.148 | RPGRIP1L | Sarah Leigh Added comment: Comment on list classification: Rating changed from green to red, as the phenotypic features associated with RPGRIP1L variants are ciliopathies. It is green on Renal ciliopathies (https://panelapp.genomicsengland.co.uk/panels/725/gene/RPGRIP1L/) and Rare multisystem ciliopathy disorders (https://panelapp.genomicsengland.co.uk/panels/150/gene/RPGRIP1L/) panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.146 | ROR2 |
Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene, where hydronephrosis is reported in Robinow syndrome autosomal dominant and in ROR2-related disorders autosomal recessive. At least 8 variants reported have been reported in Robinow syndrome recessive in the literature (PMID 10932187;19640924;18831060), however, renal anomolies were only reported in one case (PMID 15952209).; to: Comment on list classification: Associated with relevant phenotype in OMIM and as Confirmed Gen2Phen gene, where hydronephrosis is reported in Robinow syndrome autosomal dominant and in ROR2-related disorders autosomal recessive. At least 8 variants reported have been reported in Robinow syndrome, autosomal recessive 268310 in the literature (PMID 10932187;19640924;18831060), however, renal anomolies were only reported in one case (PMID 15952209). Green rating is based on Expert review by Zornitza Stark that ~10% of cases of Robinow syndrome, autosomal recessive 268310 have renal abnormalities and because of the Confirmed Gen2Phen rating. |
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| CAKUT v1.143 | ROR2 |
Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene, where hydronephrosis is reported in Robinow syndrome autosomal dominant and in ROR2-related disorders autosomal recessive. At least 8 variants reported have been reported in Robinow syndrome recessive in the literature (PMID 10932187;19640924;18831060), however, renal anomolies were only reported in one case (PMID 15952209). |
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| CAKUT v1.138 | WNT5A | Catherine Snow Added comment: Comment on list classification: WNT5A associated with Robinow syndrome. Although renal disorder is associated with syndrome limited known variants reported in literature. Lots of functional models in mice therefore rating as Amber due to lack of human variants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.134 | NIPBL | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 13 variants reported, however, there seems to be little evidence of renal involvement. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.124 | NADSYN1 | Sarah Leigh Phenotypes for gene: NADSYN1 were changed from Multiple congenital abnormalities; absent kidneys; cardiac; limb; vertebral to Vertebral, cardiac, renal, and limb defects syndrome 3 618845 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.112 | DHCR7 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green on advice from Helen Brittain (Genomics England Clinical Team). Helen notes that it meets the inclusion criteria (renal malformations as part of a wider syndromic phenotype). There are other post-natally relevant renal malformations (unilateral agenesis, hydronephrosis and cysts). It is also a gene that we have a biochemical test for, so VUSs would be easier to re-categorise than some genes. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.110 | TBX18 | Rebecca Foulger Phenotypes for gene: TBX18 were changed from to CAKUT; Renal cysts and diabetes; glomerulocystic kidney disease; hypomagneseamia; Congenital anomalies of kidney and urinary tract 2, 143400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.101 | LRP4 | Ivone Leong Added comment: Comment on list classification: New gene added by expert reviewer. LRP4 is associated with a relevant phenotype in OMIM and Gene2Phenotype, with Gene2Phenotype listing renal agenesis and renal hypoplasia as a phenotype. There are >3 unrelated cases of patients with LRP4 variants who have renal hypoplasia or renal agenesis as a feature. There is also a mouse model. Therefore there is enough evidence to support a gene-disease association for this gene to be Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.91 | JAG1 |
Ivone Leong Added comment: Comment on list classification: New gene added by expert reviewer (Chirag Patel (Genetic Health Queensland)). JAG1 is associated with a relevant disease in OMIM and Gene2Phenotype. Renal structural involvement for cases of Alagille syndrome caused by variants in the JAG1 gene is well known. Based on the expert review and literature evidence there is enough evidence to support a gene-disease assocation. Therefore this gene has been given Green status. |
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| CAKUT v1.85 | GREB1L | Ivone Leong Phenotypes for gene: GREB1L were changed from Renal hypodysplasia/aplasia 3, MIM# 617805 to Renal hypodysplasia/aplasia 3, 617805 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.81 | FGF20 | Rebecca Foulger Phenotypes for gene: FGF20 were changed from Renal hypodysplasia/aplasia 2, MIM#615721 to ?Renal hypodysplasia/aplasia 2, 615721 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.80 | FGF20 | Rebecca Foulger changed review comment from: PMID:22698282. Barak et al., 2012 identify a homozygous frameshift truncating variant (c.337delG) in FGF20, which segregated with the disorder in a consanguineous familly. Pregnancies showed anhydramnios and the fetuses had bilateral renal agenesis. All pregnancies were terminated. Mouse model shows loss of Fgf20 resulted in kidney agenesis.; to: PMID:22698282. Barak et al., 2012 identify a consanguineous family where multiple pregnancies showed anhydramnios and the fetuses had bilateral renal agenesis. DNA analysis from the initial fetus identified homozygous variants in four genes expressed during early kidney development. One of these mutations was a single base-pair deletion in exon 2 of FGF20 which segregated with the disorder within the family. All pregnancies were terminated. A mouse model shows loss of Fgf20 resulted in kidney agenesis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.80 | FAM58A | Rebecca Foulger Added comment: Comment on list classification: FAM58A added to panel and rated Green by Zornitza Stark. Updated rating from Grey to Green following literature review: sufficient cases to support gene:disease association, and renal phenotypes are common. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.79 | FAM58A | Rebecca Foulger Phenotypes for gene: FAM58A were changed from STAR syndrome, MIM# 300707 to STAR syndrome, 300707; Syndactyly, Telecanthus, Anogenital malformations and Renal malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.76 | FAM58A | Rebecca Foulger commented on gene: FAM58A: PMID:28225384 (Lefroy et al., 2017) report a 19 year old woman with STAR syndrome; phenotypes include a small left kidney and impaired renal function. The patient had a Xq28 deletion which included the whole FAM58A gene. The mother was mosaic for the deletion, and had a milder phenotype with normal renal ultrasound and renal function. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.73 | DHCR7 | Rebecca Foulger changed review comment from: Comment on list classification: Added to panel and rated Green by Zornitza Stark. Updated rating from Grey to Amber. Renal phenotypes are only seen in approximately 25% of SLOS patients, and renal anomalies are more commonly detected prenatally than postnatally (PMID:23059950) so DHCR7 is more suited to the Fetal anomalies panel.; to: Comment on list classification: Added to panel and rated Green by Zornitza Stark. Updated rating from Grey to Amber. Renal phenotypes are only seen in approximately 25% of SLOS patients, and renal anomalies are more commonly detected prenatally than postnatally (PMID:23059950) so DHCR7 is more appropriate for the Fetal anomalies panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.73 | DHCR7 | Rebecca Foulger changed review comment from: Comment on list classification: Added to panel and rated Green by Zornitza Stark. Updated rating from Grey to Amber. Renal phenotypes are only seen in approximately 25% of SLOS patients, and renal anomalies are more commonly detected prenatally than postnatally (PMID:23059950).; to: Comment on list classification: Added to panel and rated Green by Zornitza Stark. Updated rating from Grey to Amber. Renal phenotypes are only seen in approximately 25% of SLOS patients, and renal anomalies are more commonly detected prenatally than postnatally (PMID:23059950) so DHCR7 is more suited to the Fetal anomalies panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.72 | DHCR7 | Rebecca Foulger Added comment: Comment on list classification: Added to panel and rated Green by Zornitza Stark. Updated rating from Grey to Amber. Renal phenotypes are only seen in approximately 25% of SLOS patients, and renal anomalies are more commonly detected prenatally than postnatally (PMID:23059950). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.71 | DHCR7 | Rebecca Foulger commented on gene: DHCR7: PMID:9678700. Ryan et al., 1998 reviewed all known UK cases of SLOS. Half had been terminated or died in infancy. 14 (29%) had structural renal abnormalities. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.71 | DHCR7 | Rebecca Foulger commented on gene: DHCR7: PMID:23059950. Nowaczyk and Irons, 2012 note that approximately 25% of affected individuals have renal anomalies (most common being renal hypoplasia or agenesis, renal cortical cysts, hydronephrosis and structural anomalies of the collecting system). They also note that renal anomalies are amongst the phenotypes seen more commonly prenatally than postnatally. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.71 | DHCR7 | Rebecca Foulger commented on gene: DHCR7: PMID:10069707. Kratz and Kelley, 1999 report on prenatal diagnosis of SLOS. Fetal phenotypes included renal agenesis, renal pyelectasis, hydronephrosis (4 patients) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.71 | DHCR7 | Rebecca Foulger Phenotypes for gene: DHCR7 were changed from Smith-Lemli-Opitz syndrome, MIM# 270400 to Smith-Lemli-Opitz syndrome, 270400; renal agenesis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.69 | CTU2 | Rebecca Foulger Added comment: Comment on list classification: Added to panel and rated Green by Zornitza Stark. The Saudi cases all share a founder variant (PMIDs:26633546, 27480277) but a more recent study by the same authors (PMID:31301155) identifies a further 4 patients with a renal phenotype as part of DREAM‐PL syndrome, and new homozygous CTU2 variants. Therefore relevant renal phenotype and sufficient unrelated cases to support association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.68 | CTU2 | Rebecca Foulger Phenotypes for gene: CTU2 were changed from Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, MIM#618142 to DREAM‐PL syndrome; Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, 618142 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.67 | CTU2 | Rebecca Foulger commented on gene: CTU2: PMID:31301155 (Shaheen et al., 2019) show that biallelic CTU2 variants cause DREAM-PL syndrome (dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly) in a further 5 patients. 4/5 patients had a renal phenotype. These 5 patients had different variants to the previously described founder variant, including Ala403Cysfs*23, Leu63Pro, p.Ile505Argfs*41. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.64 | CHD1L | Rebecca Foulger commented on gene: CHD1L: PMID:32164334 show CNVs in genes including CHD1L in 6 CAKUT patients. One patient with bilateral renal cortical cysts and renal stones (ID 41) had a duplication of 1q21.1 encompassing CHD1L. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.61 | TFAP2A | Catherine Snow Added comment: Comment on list classification: TFAP2A identified by expert review. Phenotype for the gene disease association is mainly branchial cleft sinus defects, ocular anomalies such as microphthalmia and lacrimal duct obstruction and a dysmorphic facial appearance including cleft or pseudocleft lip/palate. However PMID: 21204207 - Genotype-phenotype Analysis of the Branchio-Oculo-Facial Syndrome states that renal anomalies, including dysplasia, agenesis,multicystic kidneys, and vesicoureteral reflux was seen in 12/34; 35% who had variants mainly in exon 4 &5 of the TFAP2A gene. Functional evidence PMID: 31160420 demonstrates that TFAP2A is involved in kidney development | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.59 | ZIC3 | Catherine Snow Added comment: Comment on list classification: ZIC3 identified by expert review for the CAKUT panel. ZIC3 is associated with VATER/VACTERL. Renal malformations is a phenotype of this disorder. Phenotypic spectrum of ZIC3 mutation carriers is quite variable, with incomplete penetrance in males however sufficient number of unrelated cases with renal malformations for this to be classed as Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.58 | GREB1L | John Sayer reviewed gene: GREB1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 29220675, 29100091; Phenotypes: renal agenesis, uterus agenesis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.58 | CENPF | Rebecca Foulger commented on gene: CENPF: Kept rating as Amber following agreement from Helen Brittain, Genomics England Clinical Team: the evidence for a congenital renal anomaly is borderline, and in view of two families only, Amber is appropriate until further families are identified. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.58 | CEP55 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Green. Gene was added to the panel and rated Green by Zornitza Stark. 3 separate variants from 3 different ethnic groups (2 of the variants are likely Founder variants), plus zebrafish model. Most homozygous nonsense variants are embryonic lethal but PMID:28295209 report viable compound het missense variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.57 | CEP55 | Rebecca Foulger Phenotypes for gene: CEP55 were changed from Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, 236500 to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, 236500; MARCH syndrome; Meckel-like syndrome; lethal CEP55-related syndromes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.55 | CEP55 | Rebecca Foulger commented on gene: CEP55: PMID:32100459 (Barrie et al., 2020) describe 7 individuals from 5 families with biallelic CEP55 variants. This is the first reported case of missense variants in CEP55 (Previously only a prenatal lethal phenotype was reported due to homozygous CEP55 nonsense variants). The authors suggest that compound het cases with nonsense and missense CEP55 variants have a different viable phenotype. Homozgyosity for a splice variant in CEP55 is compatible with life. Renal abnormality was reported in Patient 3. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.55 | CEP55 | Rebecca Foulger commented on gene: CEP55: PMID:28295209. Bondeson et al report a Swedish couple with 2 affected male fetuses homozygous for CEP55 p.Arg86*. Although the phenotype differed between fetuses, both exhibited kidney phenotypes (including renal dysplaisa). Segregation analysis supported the gene:disease association, and Haplotype analysis suggested a founder effect. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.54 | CEP55 | Rebecca Foulger commented on gene: CEP55: PMID:28264986: Frosk et al, 2017 report a Dutch-German Mennonite family with 3 affected fetuses homozygous for CEP55 nonsense variant p.Ser425* presenting with MIM:236500 including renal dysplasia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.54 | CEP55 | Rebecca Foulger Phenotypes for gene: CEP55 were changed from Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500 to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, 236500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.53 | CENPF | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Amber. Gene was added to panel and rated Green by Zornitza Stark. Although CENPF has 'probable' disease confidence in Gene2Phenotype for Stromme syndrome, there are sufficient cases in OMIM and the literature to support the gene:disease association. Hydronephrosis/renal hypoplasia is seen in at least 2 Stromme families, but the phenotype is variable. CENPF is Green on the 'Renal ciliopathies' panel (Panel #725, V1.12). Rated as Amber awaiting further clinical feedback. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.52 | CENPF | Rebecca Foulger commented on gene: CENPF: PMID:26820108 (Filges et al., 2016) describe long-term clinical follow up for siblings reported by Stromme et al. (1993) with intestingal atresia, ocular anomalis and microcephaly. They detect truncating compound het variants in CENPF in the original family (Family A) and an additional sibling pair (Family B). The original siblings (Family A) had normal renal newborn ultrasounds. The additional siblings (Family B) had Hydronephrosis/bilateral renal hypoplasia in addition to Duodenal atresia and other gastrointestinal phenotypes. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.52 | CENPF | Rebecca Foulger commented on gene: CENPF: PMID:25564561 (Waters et al., 2015) ientified a non-consagnuineous Caucasian kindred with 4 affected fetuses. Autopsy revealed phenotypes including Duodenal atresia and Bilateral renal hypolasia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.52 | CENPF | Rebecca Foulger commented on gene: CENPF: PMID:28407396 (Ozkinay et al., 2017) report a Stromme syndrome family with 2 affected individuals and a homozygous p.T1974Nfs*9 variant in CENPF. Renal phenotypes are not recorded in table 1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.51 | CENPF | Rebecca Foulger Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605 to Stromme syndrome, 243605; bilateral renal hypoplasia; Duodenal atresia; Hydronephrosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.49 | BMP7 | Rebecca Foulger Added comment: Comment on list classification: BMP7 was added to CAKUT panel and rated Red by Zornitza Stark. Updated rating from Grey to Red to match Zornitza's review: There are additional functional papers reporting a role for BMP7 in renal tissues, but only one reported family plus a mouse model. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.48 | BMP7 | Rebecca Foulger commented on gene: BMP7: PMID:7590254 (Dudley et al., 1995) report that mice lacking BMP7 display severe defects confined to the developing kidney and eye (renal dysplasia and anophthalmia at birth). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.47 | BMP4 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Amber based on a number of papers linking BMP4 variants and renal phenotypes. Penetrance isn't complete (PMID:18305125), and phenotype is variable, even within families (PMID:30568244). However a mouse model supports a renal phenotype, and functional evidence shows expression in renal tissues. Therefore rated Amber awaiting further clinical review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.46 | BMP4 | Rebecca Foulger Added comment: Comment on phenotypes: Not currently associated with a renal phenotype in OMIM or Gene2Phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.46 | BMP4 | Rebecca Foulger Phenotypes for gene: BMP4 were changed from to CAKUT; renal maldevelopment; congenital renal dysplasia; Congenital Anomaly of the Kidneys and Urinary Tract | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.43 | BMP4 | Rebecca Foulger commented on gene: BMP4: PMID:30568244 (Nixon et al., 2019) investigate a BMP4 variant ( c. 130G>T, p.(Gly44Ter) with segregated in a family with Stickler syndrome. One male (age 20) also had congenital renal dysplasia. No other family members reported kidney disease. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.43 | BMP4 |
Rebecca Foulger changed review comment from: PMID:18305125 (Weber et al., 2008) report 3 BMP4 variants in 5 unrelated Renal hypodysplasia (RH) patients (Ser91Cys, heterozygous in patients 6 and 7; Thr116Ser, heterozygous in patient 8; Asn150Lys, heterozygous in patient 9 and homozygous in patient 10). Patients were from Poland, Germany and Turkey. The father of patient 7 also had the variant but had normal renal ultrasound. The inheritance may be polygenic: the authors show expression of BMP4 in human renal tissue. PMID:19685083 (Tabatabaeifar et al., 2009) report functional evidence for these three missense mutations, and provide in vitro functional evidence in human cell lines that BMP4 mRNA is reduced in the mutants. ; to: PMID:18305125 (Weber et al., 2008) report 3 BMP4 variants in 5 unrelated CAKUT patients (Ser91Cys, heterozygous in patients 6 and 7; Thr116Ser, heterozygous in patient 8; Asn150Lys, heterozygous in patient 9 and homozygous in patient 10). Patients were from Poland, Germany and Turkey. All five affected patients presented with a spectrum of renal maldevelopment, ranging from kidney agenesis to hypoplasia and dysplasia (with or without cysts). The father of patient 7 also had the variant but had normal renal ultrasound. The inheritance may be polygenic: the authors show expression of BMP4 in human renal tissue. PMID:19685083 (Tabatabaeifar et al., 2009) report functional evidence for these three missense mutations, and provide in vitro functional evidence in human cell lines that BMP4 mRNA is reduced in the mutants. |
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| CAKUT v1.43 | BMP4 | Rebecca Foulger changed review comment from: PMID:18305125 (Weber et al., 2008) report 3 BMP4 variants in 5 unrelated Renal hypodysplasia (RH) patients (Ser91Cys, heterozygous in patients 6 and 7; Thr116Ser, heterozygous in patient 8; Asn150Lys, heterozygous in patient 9 and homozygous in patient 10). Patients were from Poland, Germany and Turkey. The father of patient 7 also had the variant but had normal renal ultrasound. The inheritance may be polygenic. the authors show expresson of BMP4 in human renal tissue.; to: PMID:18305125 (Weber et al., 2008) report 3 BMP4 variants in 5 unrelated Renal hypodysplasia (RH) patients (Ser91Cys, heterozygous in patients 6 and 7; Thr116Ser, heterozygous in patient 8; Asn150Lys, heterozygous in patient 9 and homozygous in patient 10). Patients were from Poland, Germany and Turkey. The father of patient 7 also had the variant but had normal renal ultrasound. The inheritance may be polygenic: the authors show expression of BMP4 in human renal tissue. PMID:19685083 (Tabatabaeifar et al., 2009) report functional evidence for these three missense mutations, and provide in vitro functional evidence in human cell lines that BMP4 mRNA is reduced in the mutants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.43 | BMP4 | Rebecca Foulger commented on gene: BMP4: PMID:18305125 (Weber et al., 2008) report 3 BMP4 variants in 5 unrelated Renal hypodysplasia (RH) patients (Ser91Cys, heterozygous in patients 6 and 7; Thr116Ser, heterozygous in patient 8; Asn150Lys, heterozygous in patient 9 and homozygous in patient 10). Patients were from Poland, Germany and Turkey. The father of patient 7 also had the variant but had normal renal ultrasound. The inheritance may be polygenic. the authors show expresson of BMP4 in human renal tissue. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.43 | BMP4 | Rebecca Foulger commented on gene: BMP4: PMID:23641053 (Kaku et al., 2013). Indirect Animal study. Authors studied renal expression and phenotype of Isl1 in mice. Lack of Isl1 reduced the expression of mouse Bmp4. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.43 | NADSYN1 |
Zornitza Stark gene: NADSYN1 was added gene: NADSYN1 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: NADSYN1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NADSYN1 were set to 31883644 Phenotypes for gene: NADSYN1 were set to Multiple congenital abnormalities; absent kidneys; cardiac; limb; vertebral Review for gene: NADSYN1 was set to GREEN gene: NADSYN1 was marked as current diagnostic Added comment: Five individuals from four unrelated families. Sources: Expert list |
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| CAKUT v1.43 | CHRNA3 |
Zornitza Stark gene: CHRNA3 was added gene: CHRNA3 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: CHRNA3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CHRNA3 were set to 31708116 Phenotypes for gene: CHRNA3 were set to CAKUT; dysautonomia Review for gene: CHRNA3 was set to GREEN gene: CHRNA3 was marked as current diagnostic Added comment: Five affected individuals from three unrelated families. Sources: Expert list |
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| CAKUT v1.41 | WNT5A |
Zornitza Stark gene: WNT5A was added gene: WNT5A was added to CAKUT. Sources: Expert list Mode of inheritance for gene: WNT5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: WNT5A were set to Robinow syndrome, autosomal dominant 1, MIM#180700 Review for gene: WNT5A was set to GREEN gene: WNT5A was marked as current diagnostic Added comment: Renal anomalies in about a quarter. Sources: Expert list |
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| CAKUT v1.41 | ZIC3 |
Zornitza Stark gene: ZIC3 was added gene: ZIC3 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: ZIC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ZIC3 were set to VACTERL association, X-linked, MIM# 314390 Review for gene: ZIC3 was set to GREEN Added comment: Renal malformations are a feature of VACTERL. Sources: Expert list |
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| CAKUT v1.41 | TBC1D1 |
chirag patel gene: TBC1D1 was added gene: TBC1D1 was added to CAKUT. Sources: Literature Mode of inheritance for gene: TBC1D1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TBC1D1 were set to PMID: 26572137 Phenotypes for gene: TBC1D1 were set to CAKUT Review for gene: TBC1D1 was set to GREEN Added comment: 1 heterozygous de novo frameshift variant in TBC1D1 in 1 CAKUT. 3 further CAKUT cases with three novel or rare inherited heterozygous TBC1D1 missense variants predicted to be pathogenic. TBC1D1 mutations affected Ser237-phosphorylation or protein stability and thereby act as hypomorphs. Tbc1d1 showed widespread expression in the developing murine urogenital system. A mild CAKUT spectrum phenotype, including anomalies observed in patients carrying TBC1D1 mutations, was found in kidneys of some Tbc1d1 (-/-) mice. Significantly reduced Glut4 levels were detected in kidneys of Tbc1d1 (-/-) mice and the dysplastic kidney of a TBC1D1 mutation carrier versus controls. TBC1D1 and SLC2A4 encoding GLUT4 were highly expressed in human fetal kidney. These data demonstrate heterozygous deactivating TBC1D1 mutations in CAKUT patients with a similar renal and ureteral phenotype, and provide evidence that TBC1D1 mutations may contribute to CAKUT pathogenesis, possibly via a role in glucose homeostasis. Sources: Literature |
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| CAKUT v1.41 | STRA6 |
Zornitza Stark gene: STRA6 was added gene: STRA6 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: STRA6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: STRA6 were set to Microphthalmia, syndromic 9, MIM# 601186 Review for gene: STRA6 was set to GREEN Added comment: Renal malformations are part of the phenotype. Sources: Expert list |
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| CAKUT v1.41 | SLIT2 | Zornitza Stark reviewed gene: SLIT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 26026792; Phenotypes: CAKUT; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.41 | SALL4 |
chirag patel gene: SALL4 was added gene: SALL4 was added to CAKUT. Sources: Literature Mode of inheritance for gene: SALL4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SALL4 were set to PMID: 20301547 Phenotypes for gene: SALL4 were set to SALL4- related disorders Added comment: Phenotypes include: Duane-radial ray syndrome / Okihiro syndrome; Acro-renal-ocular syndrome; and SALL4-related Holt-Oram syndrome. Acro-renal-ocular syndrome is established clinically in individuals with the following: -Radial ray malformations -Renal abnormalities that can include mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, vesico-ureteral reflux, and bladder diverticula -Ocular abnormalities that can include ocular coloboma and Duane anomaly Sources: Literature |
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| CAKUT v1.41 | ROR2 |
Zornitza Stark gene: ROR2 was added gene: ROR2 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: ROR2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ROR2 were set to Robinow syndrome, autosomal recessive, MIM# 268310 Review for gene: ROR2 was set to GREEN gene: ROR2 was marked as current diagnostic Added comment: Although genital abnormalities are a characteristic feature, renal abnormalities described in ~10% Sources: Expert list |
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| CAKUT v1.41 | NOTCH2 |
chirag patel gene: NOTCH2 was added gene: NOTCH2 was added to CAKUT. Sources: Literature Mode of inheritance for gene: NOTCH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NOTCH2 were set to PMID: 22105858 Phenotypes for gene: NOTCH2 were set to Alagille syndrome 2; OMIM #610205 Review for gene: NOTCH2 was set to GREEN Added comment: Renal abnormalities, both structural (small hyperechoic kidney, ureteropelvic obstruction, renal cysts) and functional (most commonly renal tubular acidosis), are found in 39% of affected individuals (73/187) [Kamath et al 2012b, Romero 2018]. Romero R. The renal sequelae of Alagille Syndrome as a Product of Altered Notch Signaling During Kidney Development. In: Kamath, BM and Loomes, KM, eds. Alagille Syndrome: Pathogenesis and Clinical Management. Cham, Switzerland: Springer Nature Switzerland AG; 2018:103-20. Sources: Literature |
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| CAKUT v1.41 | NIPBL |
Zornitza Stark gene: NIPBL was added gene: NIPBL was added to CAKUT. Sources: Expert list Mode of inheritance for gene: NIPBL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NIPBL were set to 8291537 Phenotypes for gene: NIPBL were set to Cornelia de Lange syndrome 1, MIM# 122470 Review for gene: NIPBL was set to GREEN gene: NIPBL was marked as current diagnostic Added comment: Renal abnormalities, primarily vesicoureteral reflux, have been reported in 12% Sources: Expert list |
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| CAKUT v1.41 | LRP4 |
Zornitza Stark gene: LRP4 was added gene: LRP4 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: LRP4 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: LRP4 were set to Cenani-Lenz syndactyly syndrome, MIM# 212780 Review for gene: LRP4 was set to GREEN gene: LRP4 was marked as current diagnostic Added comment: Renal hypoplasia/dysplasia is a recognised feature of this syndrome, and is a feature of the mouse model. Sources: Expert list |
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| CAKUT v1.41 | KMT2D |
Zornitza Stark gene: KMT2D was added gene: KMT2D was added to CAKUT. Sources: Expert list Mode of inheritance for gene: KMT2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KMT2D were set to 23535010 Phenotypes for gene: KMT2D were set to Kabuki syndrome 1, MIM# 147920 Review for gene: KMT2D was set to GREEN gene: KMT2D was marked as current diagnostic Added comment: Renal malformations are part of the phenotype. Sources: Expert list |
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| CAKUT v1.41 | KDM6A |
Zornitza Stark gene: KDM6A was added gene: KDM6A was added to CAKUT. Sources: Expert list Mode of inheritance for gene: KDM6A was set to Other Publications for gene: KDM6A were set to 23535010 Phenotypes for gene: KDM6A were set to Kabuki syndrome 2, MIM# 300867 Review for gene: KDM6A was set to GREEN Added comment: Renal malformations are a recognised feature of this syndrome. Sources: Expert list |
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| CAKUT v1.41 | JAG1 |
chirag patel gene: JAG1 was added gene: JAG1 was added to CAKUT. Sources: Literature Mode of inheritance for gene: JAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: JAG1 were set to PMID: 22105858 Phenotypes for gene: JAG1 were set to Alagille syndrome 1; OMIM #118450 Review for gene: JAG1 was set to GREEN Added comment: Renal abnormalities, both structural (small hyperechoic kidney, ureteropelvic obstruction, renal cysts) and functional (most commonly renal tubular acidosis), are found in 39% of affected individuals (73/187) [Kamath et al 2012b, Romero 2018]. Romero R. The renal sequelae of Alagille Syndrome as a Product of Altered Notch Signaling During Kidney Development. In: Kamath, BM and Loomes, KM, eds. Alagille Syndrome: Pathogenesis and Clinical Management. Cham, Switzerland: Springer Nature Switzerland AG; 2018:103-20. Sources: Literature |
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| CAKUT v1.41 | HOXA13 |
Zornitza Stark gene: HOXA13 was added gene: HOXA13 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: HOXA13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: HOXA13 were set to Hand-foot-uterus syndrome, MIM# 140000 Review for gene: HOXA13 was set to GREEN gene: HOXA13 was marked as current diagnostic Added comment: CAKUT is a feature of this condition, variable severity. Sources: Expert list |
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| CAKUT v1.41 | GREB1L |
Zornitza Stark gene: GREB1L was added gene: GREB1L was added to CAKUT. Sources: Expert list Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GREB1L were set to 29100091 Phenotypes for gene: GREB1L were set to Renal hypodysplasia/aplasia 3, MIM# 617805 Review for gene: GREB1L was set to GREEN gene: GREB1L was marked as current diagnostic Added comment: At least 16 families described, and mouse model supports gene-disease association. Sources: Expert list |
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| CAKUT v1.41 | GPC3 |
Zornitza Stark gene: GPC3 was added gene: GPC3 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: GPC3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: GPC3 were set to Simpson-Golabi-Behmel syndrome, type 1 312870 Review for gene: GPC3 was set to GREEN gene: GPC3 was marked as current diagnostic Added comment: Nephromegaly, multicystic kidneys, hydronephrosis, hydroureter, and duplicated ureters are described features of this syndrome. Sources: Expert list |
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| CAKUT v1.41 | FGF20 |
Zornitza Stark gene: FGF20 was added gene: FGF20 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: FGF20 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FGF20 were set to 22698282 Phenotypes for gene: FGF20 were set to Renal hypodysplasia/aplasia 2, MIM#615721 Review for gene: FGF20 was set to AMBER Added comment: Multiple affected fetuses in a consanguineous family; functional data. Sources: Expert list |
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| CAKUT v1.41 | FAM58A |
Zornitza Stark gene: FAM58A was added gene: FAM58A was added to CAKUT. Sources: Expert list Mode of inheritance for gene: FAM58A was set to Other Publications for gene: FAM58A were set to 28225384; 18297069 Phenotypes for gene: FAM58A were set to STAR syndrome, MIM# 300707 Review for gene: FAM58A was set to GREEN gene: FAM58A was marked as current diagnostic Added comment: XL-dominant disorder, multiple affected families reported, renal malformation are part of the phenotype. Note deletions and sequence variants reported. Sources: Expert list |
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| CAKUT v1.41 | EXOC3L2 |
chirag patel gene: EXOC3L2 was added gene: EXOC3L2 was added to CAKUT. Sources: Literature Mode of inheritance for gene: EXOC3L2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOC3L2 were set to PMID: 30327448, 28749478, 27894351 Phenotypes for gene: EXOC3L2 were set to Dandy-Walker malformation; renal dysplasia; bone marrow failure Review for gene: EXOC3L2 was set to GREEN Added comment: Four individuals from two unrelated families with brain, kidney and bone marrow abnormalities; another described as part of fetal autopsy series, and another in a ciliopathy cohort. Sources: Literature |
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| CAKUT v1.41 | DHCR7 |
Zornitza Stark gene: DHCR7 was added gene: DHCR7 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DHCR7 were set to 3812577; 10069707; 23059950; 9678700 Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome, MIM# 270400 gene: DHCR7 was marked as current diagnostic Added comment: Approximately 25% of affected individuals have renal anomalies, most commonly renal hypoplasia or agenesis, renal cortical cysts, hydronephrosis, and structural anomalies of the collecting system [Curry et al 1987, Ryan et al 1998, Kratz & Kelley 1999, Nowaczyk et al 2001]. Sources: Expert list |
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| CAKUT v1.41 | CTU2 |
Zornitza Stark gene: CTU2 was added gene: CTU2 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CTU2 were set to 27480277; 26633546; 31301155 Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, MIM#618142 Review for gene: CTU2 was set to GREEN gene: CTU2 was marked as current diagnostic Added comment: Multiple families reported though some share the same founder variant. Sources: Expert list |
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| CAKUT v1.41 | CEP55 |
Zornitza Stark gene: CEP55 was added gene: CEP55 was added to CAKUT. Sources: Expert list Mode of inheritance for gene: CEP55 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CEP55 were set to 30622327 Phenotypes for gene: CEP55 were set to Multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia, and hydranencephaly, MIM# 236500 Review for gene: CEP55 was set to GREEN gene: CEP55 was marked as current diagnostic Added comment: Three families and a zebrafish model support gene-disease association. Sources: Expert list |
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| CAKUT v1.41 | CENPF |
Zornitza Stark gene: CENPF was added gene: CENPF was added to CAKUT. Sources: Expert list Mode of inheritance for gene: CENPF was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CENPF were set to Stromme syndrome, MIM#243605 Review for gene: CENPF was set to GREEN Added comment: Renal hypodysplasia and hydronephrosis are a feature of this syndrome. Sources: Expert list |
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| CAKUT v1.34 | RET | Eleanor Williams Phenotypes for gene: RET were changed from Renal Adysplasia; Multiple endocrine neoplasia IIA, 171400Medullary thyroid carcinoma, 155240Multiple endocrine neoplasia IIB, 162300Central hypoventilation syndrome, congenital, 209880Pheochromocytoma, 171300Renal agenesis, 191830{Hirschsprung disease, susceptibility to, 1}, 142623 to Renal Adysplasia; Multiple endocrine neoplasia IIA, 171400; Medullary thyroid carcinoma, 155240; Multiple endocrine neoplasia IIB, 162300; Central hypoventilation syndrome, congenital, 209880; Pheochromocytoma, 171300; Renal agenesis, 191830; {Hirschsprung disease, susceptibility to, 1}, 142623 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.33 | NPHP3 | Eleanor Williams Phenotypes for gene: NPHP3 were changed from Nephronophthisis 3, 604387Renal-hepatic-pancreatic dysplasia 1, 208540Meckel syndrome 7, 267010; Renal-Hepatic-Pancreatic Dysplasia to Nephronophthisis 3, 604387; Renal-hepatic-pancreatic dysplasia 1, 208540; Meckel syndrome 7, 267010; Renal-Hepatic-Pancreatic Dysplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.32 | EYA1 | Eleanor Williams Phenotypes for gene: EYA1 were changed from Branchiootorenal syndrome 1, with or without cataracts, 113650Anterior segment anomalies with or without cataract, 113650Branchiootic syndrome 1, 602588Otofaciocervical syndrome, 166780; Branchiootorenal Spectrum Disorders to Branchiootorenal syndrome 1, with or without cataracts, 113650; Anterior segment anomalies with or without cataract, 113650; Branchiootic syndrome 1, 602588; Otofaciocervical syndrome, 166780; Branchiootorenal Spectrum Disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.31 | BSND | Eleanor Williams Phenotypes for gene: BSND were changed from Bartter syndrome, type 4a, 602522Sensorineural deafness with mild renal dysfunction, 602522 to Bartter syndrome, type 4a, 602522; Sensorineural deafness with mild renal dysfunction, 602522 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.30 | AGTR1 | Eleanor Williams Phenotypes for gene: AGTR1 were changed from Renal Tubular Dysgenesis; Hypertension, essential, 145500Renal tubular dysgenesis, 267430 to Renal Tubular Dysgenesis; Hypertension, essential, 145500; Renal tubular dysgenesis, 267430 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CAKUT v1.25 | ISCA-37432-Loss |
Louise Daugherty Region: ISCA-37432-Loss was added Region: ISCA-37432-Loss was added to CAKUT. Sources: ClinGen,Expert Review Green Mode of inheritance for Region: ISCA-37432-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for Region: ISCA-37432-Loss were set to RCAD syndrome; utero-vaginal atresia; Schizophrenia; 614527; delayed development, intellectual disability; Renal cysts and diabetes syndrome; Autism Spectrum Disorder; Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome in females; Chromosome 17q12 deletion syndrome; global developmental delay |
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