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Paediatric disorders - additional genes v1.98 FGF5 Eleanor Williams changed review comment from: This gene was originally added to the DDG2P panel but this gene is not present in the Gene2Phenotype resource. After review by a Genomics England clinician it was decided that this may be the best place for this gene as there is no specific hypertrichosis panel. Rating amber but with a recommendation for green rating if after GMS review it is considered appropriate for this panel.; to: This gene was originally added to the DDG2P panel but this gene is not present in the Developmental Disorders panel in the Gene2Phenotype resource which DDG2P panel reflects.

After review by a Genomics England clinician it was decided that this may be the best place for this gene as there is no specific hypertrichosis panel. Rating amber but with a recommendation for green rating if after GMS review it is considered appropriate for this panel.
Paediatric disorders - additional genes v1.96 ACE Arina Puzriakova Tag for-review was removed from gene: ACE.
Paediatric disorders - additional genes v1.96 ACE Sarah Leigh commented on gene: ACE
Paediatric disorders - additional genes v1.95 ACE Arina Puzriakova Source Expert Review Green was added to ACE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.87 FOXP4 Ivone Leong gene: FOXP4 was added
gene: FOXP4 was added to Paediatric disorders - additional genes. Sources: Literature
Q2_21_phenotype tags were added to gene: FOXP4.
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to AMBER
Added comment: This gene is associated with a phenotype in Gene2Phenotype but not in OMIM.

This gene is present as an Amber gene on the Intellectual disability panel (Version 3.1052) with the following reviews:

"This gene is a little bit difficult to place, may be Green on Fetal Anomalies panel? Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays, hence Amber rating here. Sources: Literature
Zornitza Stark (Australian Genomics), 4 Nov 2020"

"Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). As ID is not present in the majority of affected patients, and the affected individuals only show mild ID, this gene has been given an Amber rating.
Ivone Leong (Genomics England Curator), 4 Dec 2020"

After discussion with the Genomics England Clinical Team it was decided that this gene should be added to this panel as an Amber gene and subject to review by the GMS specialist group.
Sources: Literature
Paediatric disorders - additional genes v1.69 NHLRC2 Eleanor Williams gene: NHLRC2 was added
gene: NHLRC2 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: NHLRC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC2 were set to 29423877; 32435055
Phenotypes for gene: NHLRC2 were set to FINCA syndrome OMIM:618278
Review for gene: NHLRC2 was set to GREEN
Added comment: PMID: 29423877 Uusimaa et al 2018 - report 3 patients from 2 unrelated non-consanguineous Finnish families in which the children were born asymptomatic but by 2 months of age they had developed a progressive multi-organ disorder. The main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. All three patients were found using WES to be compound heterozygous for NM_198514:c.442G>T, p.Asp148Tyr and c.601_602delAG, p.Arg201GlyfsTer6. Segregation data for both families is provided. The family history of the two families, traced back 7–9 generations, showed that they did not have common ancestors. Both variants are rare in both Finnish (Sequencing Initiative Suomi - 0.003 and 0.0001 respectively) and non-Finnish populations (Exac). Patient fibroblasts expressed only mRNA with the c.442G>T missense variant, and at low levels. Development of Nhlrc2 null mice stalled before the morula stage. Morpholino knockdown of nhlrc2 in zebrafish embryos showed that nhlrc2 has a role in cellular integrity of the central nervous system during development.

PMID: 32435055 - Brodsky et al 2020 - report a 2 year old Ukranian patient with FINCA syndrome who was found by WES to have compound heterozygous variants in NHLRC2 (c.442T>G, p.D148Y and c.428C>A, p.H143P). The c.428C>A variant is not found in the gnomAD database. Each parent was a carrier for one of the variants.
Sources: Literature
Paediatric disorders - additional genes v1.64 PIGQ Sarah Leigh Added comment: Comment on phenotypes: According to Joanna Peas-Welch (OMIM), Multiple congenital anomalies-hypotonia-seizures syndrome-4 (MCAHS4) will replace Epileptic encephalopathy, early infantile, 77, OMIM:618548 as the name for this phenotype (12/11/2020).
Paediatric disorders - additional genes v1.32 CHRNA3 Rebecca Foulger changed review comment from: PMID:31708116 (Mann et al., 2019) identify 3 different biallelic variants in CHRNA2 in 5 individuals from 3 unrelated families with functional lower urinary tract obstruction and secondary CAKUT. All 3 variants impair acetylcholine signaling. The truncating variants p.Thr337Asnfs∗81 and p.Ser340∗ led to impaired plasma membrane localization of CHRNA3. The third variant is an essential splice site variant. None of the variants were present in gnomAD.; to: PMID:31708116 (Mann et al., 2019) identify 3 different biallelic variants in CHRNA3 in 5 individuals from 3 unrelated families with functional lower urinary tract obstruction and secondary CAKUT. All 3 variants impair acetylcholine signaling. The truncating variants p.Thr337Asnfs∗81 and p.Ser340∗ led to impaired plasma membrane localization of CHRNA3. The third variant is an essential splice site variant. None of the variants were present in gnomAD.
Paediatric disorders - additional genes v1.31 AGTR1 Rebecca Foulger commented on gene: AGTR1: PMID:16116425. Gribouval et al. 2005 studied 9 families (11 indivs) with AR renal tubular dysgenesis, and found variants in REN, AGT, ACE or AGTR1.
Paediatric disorders - additional genes v1.24 ACE Rebecca Foulger Classified gene: ACE as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.24 ACE Rebecca Foulger Added comment: Comment on list classification: Key papers report renal tubular dysgenesis. In absence of additional morphological features, keep Amber awaiting GLH review.
Paediatric disorders - additional genes v1.24 ACE Rebecca Foulger Gene: ace has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.23 ACE Rebecca Foulger commented on gene: ACE: PMID:30058238 (Bhowmik et al., 2018) report a 32-week old fetus with severe early onset oligohydramnios. A similarly affected sibling was reported from a previous pregnancy. Exome sequencing revealed a homozygous 3' splice-site variant in intron 17 of ACE gene, which confirmed AR renal tubular dysgenesis. It also facilitated prenatal diagnosis in a subsequent pregnancy.
Paediatric disorders - additional genes v1.23 ACE Rebecca Foulger commented on gene: ACE: PMID:16116425. Gribouval et al. 2005 studied 9 families (11 indivs) with AR renal tubular dysgenesis, and found variants in REN, AGT, ACE or AGTR1.
Paediatric disorders - additional genes v1.22 CHRNA3 Rebecca Foulger commented on gene: CHRNA3: PMID:31708116 (Mann et al., 2019) identify 3 different biallelic variants in CHRNA2 in 5 individuals from 3 unrelated families with functional lower urinary tract obstruction and secondary CAKUT. All 3 variants impair acetylcholine signaling. The truncating variants p.Thr337Asnfs∗81 and p.Ser340∗ led to impaired plasma membrane localization of CHRNA3. The third variant is an essential splice site variant. None of the variants were present in gnomAD.
Paediatric disorders - additional genes v1.21 AGT Rebecca Foulger commented on gene: AGT: PMID:16116425. Gribouval et al. 2005 studied 9 families (11 indivs) with AR renal tubular dysgenesis, and found variants in REN, AGT, ACE or AGTR1.
Paediatric disorders - additional genes v1.18 ACE Rebecca Foulger Publications for gene: ACE were set to 16116425; 22095942
Paediatric disorders - additional genes v1.17 ACE Rebecca Foulger changed review comment from: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.; to: Added 'for-review' tag: Requires GLH review for inclusion on Paediatric disorders panel: whether CAKUT phenotype presents alongside additional congenital malformations.
Paediatric disorders - additional genes v1.17 ACE Rebecca Foulger Publications for gene: ACE were set to
Paediatric disorders - additional genes v1.5 ACE Rebecca Foulger Classified gene: ACE as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.5 ACE Rebecca Foulger Gene: ace has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.4 ACE Rebecca Foulger commented on gene: ACE: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 ACE Rebecca Foulger Tag for-review tag was added to gene: ACE.
Paediatric disorders - additional genes v1.4 ACE Rebecca Foulger commented on gene: ACE
Paediatric disorders - additional genes v1.3 ACE Rebecca Foulger gene: ACE was added
gene: ACE was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: ACE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACE were set to CAKUT; Renal Tubular Dysgenesis
Paediatric disorders - additional genes v0.23 ABL1 Helen Brittain gene: ABL1 was added
gene: ABL1 was added to Paediatric disorders - additional genes. Sources: Literature
missense tags were added to gene: ABL1.
Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ABL1 were set to 28288113
Phenotypes for gene: ABL1 were set to Congenital heart defects and skeletal malformations syndrome 617602
Penetrance for gene: ABL1 were set to unknown
Mode of pathogenicity for gene: ABL1 was set to Other
Review for gene: ABL1 was set to GREEN
Added comment: "4 unrelated families who exhibited dysmorphic facial features, congenital heart disease, skeletal abnormalities, joint problems, failure to thrive, gastrointestinal problems, and male genital anomalies. In younger children, dysmorphic features included broad forehead, small nose, deep-set eyes, and small chin, whereas in older patients, the face appeared elongated, with a narrow maxilla, long and narrow nose, and pointed chin. Common skeletal abnormalities included pectus excavatum, scoliosis, finger contractures, and hindfoot deformity. Congenital heart defects included atrial and ventricular septal defects, and in older patients, aortic root dilation."

Sufficient cases for a green rating. Note that two missense variants have been reported to date - unclear on mode of pathogenicity.
Sources: Literature