Intellectual disability - microarray and sequencing
Gene: KCNQ3Comment on list classification: Promoted from amber to green, based on the expert reviews already provided. There are also >3 unrelated cases of patients with different variants in the KCNQ3 gene who have the described phenotype.Created: 14 Feb 2019, 4:33 p.m.
As commented in PMID: 24851285 (Clinical description section) intellectual disability is a feature of the KCNQ3-related disorders. At least 5 individuals falling into the BFNE subtype and others falling into the so-called "KCNQ3-related developmental disability" subtype had ID. The following publications are cited by the authors - PMID: 24375629, 25524373, 23934111, 28135719.
The gene is included in the DD panel of G2P, associated with KCNQ3 syndrome.
KCNQ3 is included in gene panels for intellectual disability offered by diagnostic laboratories (incl. Radboudumc).
Therefore, this gene could be considered for upgrade to green or could remain amber until further details on the phenotype become available.Created: 18 Dec 2018, 2:06 a.m.
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Changed Red to Amber from external expert review and further publications to support gene-disease association- the predominate phenotype is epilepsy with delayed developmental delay, although in PMID: 28135719 supplementary PenIcons, only 2 of the 4 cases for KCNQ3 had HPO term severe Intellectual disability so upgraded gene to Amber and not GreenCreated: 30 Jul 2018, 5:04 p.m.
Comment on publications: from external review added DDD paper. Prevalence and architecture of de novo mutations in developmental disorders (2017) PMID: 28135719Created: 30 Jul 2018, 5:01 p.m.
At least 4 variants also reported in the DDD paper, merits at least Amber.Created: 23 Jul 2018, 4:47 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Variants in this GENE are reported as part of current diagnostic practice
Variants in this gene are strongly associated with epilepsy and epilepsy syndromes. There is some evidence that shows inheritance of an epilepsy phenotype alongside a mild intellectual disability phenotype in two individuals in one family (25524373). In PMID 20384724, a family with seizures and ID are described, however the microduplication described does not appear to affect the KCNQ3 gene (no variant was detected). In PMID 25982755, patients from only 3 families in the study had intellectual disability, and none have any detected variation in KCNQ3. In PMID , there is a mention on KCNQ3-related disorder which is noted to have individuals who present with ID with or without seizures. Howevr it notes that little clinical information is available and does not state any family cases.Created: 31 Oct 2017, 10:36 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
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_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known;in_omim_20150205_epilepsies . Main mutation mechanism : NACreated: 27 Jul 2017, 7:01 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : find_uk10k; gilissen_2014_known; omim_20150205_epilepsies; sfari_20150206; Nijmegen_ID_candidates; GEL_ID_red_20160217; neuro_20160418_strict; NA. 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, 12:42 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Gene: kcnq3 has been classified as Green List (High Evidence).
Source Victorian Clinical Genetics Services was added to KCNQ3.
Gene: kcnq3 has been classified as Amber List (Moderate Evidence).
Publications for gene: KCNQ3 were set to 25524373; 20384724; 25982755; 28135719
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.
Model of inheritance for gene KCNQ3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene KCNQ3 was set to ['25524373', ' 20384724', ' 25982755']
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
KCNQ3 was added to Intellectual disabilitypanel. Sources: Expert Review Red
KCNQ3 was created by ellenmcdonagh