Intellectual disability - microarray and sequencing
Gene: GPSM2The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.
Panel Version: 3.1510
Comment on list classification: Leaving this gene as green just now, but as there are only 2 families out of 19 in which mild cognitive delay is seen then the recommendation would be to rate this gene amber. This gene should be reviewed at the next GMS update.Created: 8 Oct 2020, 4:12 p.m. | Last Modified: 8 Oct 2020, 4:12 p.m.
Panel Version: 3.404
Associated with Chudley-McCullough syndrome604213 in OMIM
Summary: From 19 reported families, 3 individuals from 2 families showed cognitive delay.
PMID: 27180139 - Hemzeh et al 2016 - report two brothers from a Yemeni family who were diagnosed clinically with CMS then tested for GPSM2 mutations using Sanger sequencing. A homozygous mutation in GPSM2 was found in both brothers (c.1055C > A) leading to a truncating protein change; (p.Ser352*). The 12 year old brother showed cognitive delay, noted by the inability to tell the time in minutes, or to follow complex commands. The 11 year old brother could speak in sentences but with poor articulation, and could not respond to complex commands. The poor articulation was thought to be due to late cochlear implant surgery.
PMID: 23494849 - Almomani et al 2013 - report three patients from two unrelated Dutch families with CMS were investigated in which the same c.1473delG variant observed in 4 of the Menonite families by Doherty et al was observed. All three patients had normal cognitive abilities.
PMID: 22578326 - Doherty et al 2012 - report on 5 Menonite, 1 European-American, 1 Dutch and 1 Mexican-American family in which probands had severe/profound hearing loss and ventriculomegaly (total of 12 affected individuals). They also look again at the patients reported with autosomal recessive nonsyndromic deafness (DFNB82) by Walsh et al 2010 (PMID: 20602914, 1 proband ina Pakistani family) and Yariz et al 2012 (PMID: 21348867, 3 probands in a Turkish family) who they found had brain abnormalities consistent with with a diagnosis of Chudley-McCullough syndrome.
Oout of the 16 patients reported, only one had developmental issues beyond what is typically seen in individuals with severe hearing loss.
- -Created: 8 Oct 2020, 4:06 p.m. | Last Modified: 8 Oct 2020, 4:09 p.m.
Panel Version: 3.401
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
ID is not typically a feature.Created: 6 Feb 2020, 9 p.m. | Last Modified: 6 Feb 2020, 9 p.m.
Panel Version: 3.0
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Chudley-McCullough syndrome, MIM#604213
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
DEAFNESS AUTOSOMAL RECESSIVE TYPE 82
Publications
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 . Main mutation mechanism : Loss of functionCreated: 27 Jul 2017, 6:25 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; 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, 12:34 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Comment on list classification: Confirmed DD geneCreated: 7 Feb 2016, 8:54 p.m.
Tag for-review was removed from gene: GPSM2.
Source Expert Review Amber was added to GPSM2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Gene: gpsm2 has been classified as Green List (High Evidence).
Tag for-review tag was added to gene: GPSM2.
Phenotypes for gene: GPSM2 were changed from DEAFNESS AUTOSOMAL RECESSIVE TYPE 82 to Chudley-McCullough syndrome, 604213
Publications for gene: GPSM2 were set to 22578326
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.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
GPSM2 was added to Intellectual disabilitypanel. Sources: Expert Review Amber
GPSM2 was created by ellenmcdonagh