Intellectual disability
Gene: CA2
Comment on phenotype. Reviewed literature and databases again due to Red review left by expert reviewer. However, there is still substantial evidence to support this gene being Green on the ID panel.
Carbonic anhydrase II deficiency syndrome is an autosomal recessive disorder that produces osteopetrosis, renal tubular acidosis, and cerebral calcification. Other features include mental retardation (seen in over 90 percent of reported cases), growth failure, and dental malocclusion. The carbonic anhydrase II gene is 20 kb, contains seven exons, and maps to chromosome 8q22. Sixteen distinct mutations have been identified in 110 reported patients. Nearly 65 percent of affected patients are homozygous for a splice junction mutation at the 5′ end of exon 2. Because of its prevalence among families of Arabic descent from Kuwait, Saudi Arabia, and North Africa, this mutation has been designated the “Arabic mutation” PMID:1301935. The second recurrent mutation, a frameshift in exon 7, is most prevalent in Caribbean Hispanic populations. The third recurrent mutation is His 107 toTyr, the first reported mutation. This mutation is due to a C to T transition in exon 3 and has been found in Belgian, Italian, Japanese and American patients (PMID: 1928091, 8834238, 1542674).Created: 13 Aug 2018, 2:25 p.m.
From Gene2Phenotype: This is a confirmed biallelic gene for OSTEOPETROSIS AUTOSOMAL RECESSIVE TYPE 3. Patients in Decipher where the Pathogenicity is Pathogenic, all have intellectual disability/global developmental delay.Created: 13 Aug 2018, 12:40 p.m.
Comment on publications: added publications suggested by external reviewers to support ID phenotypeCreated: 13 Aug 2018, 12:15 p.m.
Definitely a green gene, but is this type of osteopetrosis associated with intellectual disability?Created: 14 Jun 2018, 1:54 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known . Main mutation mechanism : Loss of functionCreated: 27 Jul 2017, 5:14 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; gilissen_2014_known; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation TrustCreated: 19 Jul 2017, 12:08 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Publications for gene: CA2 were set to 25529582; 24896178; 12566520; 1301935; 8127074; 5041390; 16265785; 28509178; 15300855; 8834238; 1928091
Publications for gene: CA2 were set to 25529582; 24896178; 12566520; 1301935; 8127074; 5041390; 16265785; 28509178; 15300855
Publications for gene: CA2 were set to 25529582; 24896178; 12566520; 1301935; 8127074; 5041390; 16265785; 28509178
Phenotypes for gene: CA2 were set to Osteopetrosis, autosomal recessive 3, with renal tubular acidosis, 259730; OSTEOPETROSIS AUTOSOMAL RECESSIVE TYPE 3 (OPTB3); carbonic anhydrase II deficiency; intellectual disability
Publications for gene: CA2 were set to 25529582; 24896178; 12566520; 1301935; 8127074; 5041390; 16265785
Publications for gene: CA2 were set to 25529582; 24896178; 12566520; 1301935; 8127074; 5041390
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
CA2 was added to Intellectual disabilitypanel. Source: Expert Review Green
CA2 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen