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Intellectual disability - microarray and sequencing v5.107 | ITPR1 |
Tracy Lester edited their review of gene: ITPR1: Added comment: PMID:29925855 - All 7 EOA patients with ITPR1 de novo variants (3 from cohort #1; 4 from cohort #2) presented with infantile onset cerebellar ataxia starting before the age of 2 years, including delayed motor milestones (Table 2). Cognitive deficits of variable degree were observed in 3 out of 4 patients where this information was available, reaching from only mild dyscalculia (P2) to severe intellectual disability with a speech vocabulary of only a few words (P7 at age 12 years). In contrast, patient P1 showed normal intelligence with an IQ of 97. PMID:27108797 - Here, we report that both recessive and dominant ITPR1 mutations cause Gillespie syndrome. ITPR1 is a predominant isoform in the brain among the three types of ITPRs and is strongly expressed in cerebellar Purkinje cells.31 Mice with complete homozygosity for Itpr1 ablation suffer from severe epilepsy and ataxia and die either in utero or before weaning.32 Consistently, ITPR1 mutations have been reported to cause cerebellar diseases including late-onset spinocerebellar ataxia type 15 (SCA15 [MIM: 606658]),33 congenital nonprogressive spinocerebellar ataxia and mild cognitive impairment (SCA29 [MIM: 117360]),34 infantile-onset cerebellar ataxia with mild cognitive deficit,35 and childhood-onset ataxic cerebellar palsy with moderate intellectual disability36 (see ITPR1 schematic diagram in Figure 3A). Affected individuals had similar iris anomalies and neonatal ataxia with progressive cerebellar atrophy (Figure 2). Moderate to severe intellectual disabilities were noted in the three individuals with recessive mutations (F1:II1, F2:II1, and F3:II1; Table 1). In contrast, the affected individual F4:II1 aged 18 years and harboring the de novo c.7687_7689del mutation was reported to have normal intelligence (Table 1). As de novo variants are associated with ID/DD the inheritance should be updated to be BOTH AD and AR.; Set current diagnostic: yes |
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Intellectual disability - microarray and sequencing v3.1535 | BRCA2 | Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Fanconi anemia, complementation group D1: FANCD1 OMIM: 605724 to Fanconi anemia, complementation group D1, OMIM:605724 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1514 | ABCA2 | Arina Puzriakova Tag for-review was removed from gene: ABCA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1510 | ABCA2 | Sarah Leigh commented on gene: ABCA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.1509 | ABCA2 |
Arina Puzriakova Source Expert Review Green was added to ABCA2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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Intellectual disability - microarray and sequencing v3.795 | BRCA2 | Sarah Leigh Source: Expert Review Amber was removed from gene: BRCA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.643 | SMARCA2 | Arina Puzriakova Phenotypes for gene: SMARCA2 were changed from Nicolaides-Baraitser syndrome, 601358; COFFIN SIRIS to Nicolaides-Baraitser syndrome, OMIM:601358; Coffin-siris syndrome; Blepharophimosis intellectual disability syndrome | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.642 | SMARCA2 | Arina Puzriakova Publications for gene: SMARCA2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.534 | ABCA2 | Arina Puzriakova Phenotypes for gene: ABCA2 were changed from Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808 to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM:618808; Intellectual developmental disorder with poor growth and with or without seizures or ataxia, MONDO:0032930 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.533 | ABCA2 | Arina Puzriakova Tag for-review tag was added to gene: ABCA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.533 | ABCA2 | Arina Puzriakova Classified gene: ABCA2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.533 | ABCA2 | Arina Puzriakova Gene: abca2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.532 | ABCA2 | Arina Puzriakova reviewed gene: ABCA2: Rating: ; Mode of pathogenicity: None; Publications: 30237576, 29302074, 31047799; Phenotypes: Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM: 618808; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.201 | SMARCA2 | Konstantinos Varvagiannis reviewed gene: SMARCA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 32694869; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v3.170 | ABCA2 |
Konstantinos Varvagiannis gene: ABCA2 was added gene: ABCA2 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799 Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, 618808 Penetrance for gene: ABCA2 were set to Complete Review for gene: ABCA2 was set to GREEN Added comment: Biallelic pathogenic ABCA2 variants cause Intellectual developmental disorder with poor growth and with or without seizures or ataxia (MIM 618808). There are 3 relevant publications (01-07-2020) : - Maddirevula et al [2019 - PMID: 30237576] described briefly 2 unrelated subjects (16-2987, 16DG0071) both DD and seizures among other manifestations. - Hu et al [2019 - PMID: 29302074] reported 3 sibs (M8600615 - III:1-3) born to consanguineous parents (M8600615 - III:1-3) with DD/ID (formal confirmation of moderate ID, in those (2) evaluated). One also presented with seizures. - Aslam and Naz [2019 - PMID: 31047799] provided clinical details on 2 siblings born to consanguineous parents. ID was reported for the older sib but was absent in the younger one. Seizures were not part of the phenotype. All subjects harbored biallelic pLoF variants. N.B. : Steinberg et al [2015 - PMID: 25773295], within a cohort of patients with ALS, identified one with biallelic ABCA2 variants. As however Aslam and Naz comment, this person harbored a single pathogenic variant, with a second one rather unlikely to be pathogenic due to high allele frequency. Overall this gene can be considered for inclusion with green rating in both ID and epilepsy panels (each in >=3 unrelated individuals). Sources: Literature |
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Intellectual disability - microarray and sequencing v3.170 | HERC2 |
Konstantinos Varvagiannis edited their review of gene: HERC2: Added comment: Please consider upgrading this gene to green in the current panel based on the following updated review (13-07-2020): Biallelic pathogenic HERC2 variants cause Mental retardation, autosomal recessive 38 (MIM 615516). The current review is based mostly on the information provided by Elpidorou et al (2020 - PMID: 32571899) summarizing the findings in several affected individuals as published in the literature. ID was a universal feature among them (27/27) and seizures were reported in some (9/27): - 22 subjects from Amish/Mennonite families were homozygous for p.Pro594Leu [NM_004667.5(HERC2):c.1781C>T] (Puffenberger et al 2012 - PMID: 23065719, Harlalka et al 2013 - PMID: 23243086, Abraham et al - PMID: 30902390) - 2 additional patients were homozygous for another missense SNV [NM_004667.5(HERC2):c.4625G>A - p.Arg1542His] (Abraham et al 2019 - PMID: 30902390) - 3 sibs born to consanguineous parents, homozygous for NM_004667.5:c.13767_13770delTGAA - p.(Asn4589LysTer4598)] as described by Elpidorou et al. - 1 male homozygous 286 kb deletion spanning several 5' exons of HERC2 as well as the first exons of OCA2 was described by Morice-Picard et al (2016 - PMID: 27759030). Despite a neurological presentation (axial hypotonia, peripheral hypertonia, extrapyramidal symptoms and uncoordinated movements) further information was not available. Apart from the cases summarized by Elpidorou et al, there have been few additional ones e.g. : - Trujillano et al (2017 - PMID: 27848944) reported briefly on a patient, homozygous for NM_004667.5:c.4676-1G>A displaying seizures, hypotonia, global DD, "Encephalopathy" and abnormality of the liver. - Yavarna et al (2015 - PMID: 26077850) provided few details with on an individual with primarily 'neurocognitive' phenotype but rather atypical presentation (MRI abnormalities, TGA, VSD, renal anomaly, growth retardation, hearing loss) due to p.Q3164X variant (recessive inheritance was specified). Several lines of evidence support an important role for the protein encoded (an E3 ubiquitin protein ligase, interacting also with UBE3A, involved in several cellular processes incl. cell cycle regulation, spindle formation during mitosis, mitochondrial functions, DNA damage responses by targeting proteins such as XPA) as well as the effect of the reported variants (mRNA studies, Western blot, detection of a fusion transcript in the case of the deletion, etc). Individuals from the Amish families displayed Angelman-like features (in line with HERC2-UBE3A interaction) with - among others - gait instability. Mouse models recapitulate some of these features (e.g. the movement disorder) as extensively discussed by Abraham et al. Overall this gene can be included in the ID and epilepsy panels with green rating. -----; Changed rating: GREEN; Changed publications: 23065719, 23243086, 30902390, 32571899, 27848944, 26077850, 27759030 |
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Intellectual disability - microarray and sequencing v2.927 | ISCA2 | Ivone Leong Classified gene: ISCA2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.927 | ISCA2 | Ivone Leong Gene: isca2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.893 | ISCA2 | Ivone Leong Tag founder-effect tag was added to gene: ISCA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.889 | ISCA2 | Ivone Leong Publications for gene: ISCA2 were set to 25539947; 29297947; 29359243; 29122497; 28356563 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.888 | ISCA2 | Ivone Leong Publications for gene: ISCA2 were set to 25539947, 29297947, 29359243 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.887 | ISCA2 | Ivone Leong Phenotypes for gene: ISCA2 were changed from Multiple mitochondrial dysfunctions syndrome 4 to Multiple mitochondrial dysfunctions syndrome 4, 616370 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.468 | SMARCA2 | Louise Daugherty Source Victorian Clinical Genetics Services was added to SMARCA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing v2.468 | ISCA2 | Louise Daugherty Source Victorian Clinical Genetics Services was added to ISCA2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | CA2 | Louise Daugherty commented on gene: CA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | CA2 | Louise Daugherty edited their review of gene: CA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | CA2 | Zornitza Stark reviewed gene: CA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | SMARCA2 | BRIDGE consortium edited their review of SMARCA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | CA2 | BRIDGE consortium edited their review of CA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | BRCA2 | BRIDGE consortium edited their review of BRCA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | SMARCA2 | BRIDGE consortium edited their review of SMARCA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | CA2 | BRIDGE consortium commented on CA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | BRCA2 | BRIDGE consortium edited their review of BRCA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | BRCA2 | Louise Daugherty classified BRCA2 as amber | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | BRCA2 | Louise Daugherty commented on BRCA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | SMARCA2 | BRIDGE consortium reviewed SMARCA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | CA2 | BRIDGE consortium reviewed CA2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Intellectual disability - microarray and sequencing | BRCA2 | BRIDGE consortium reviewed BRCA2 |