Intellectual disability - microarray and sequencing
Gene: IQSEC2The mode of inheritance of this gene has been updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.
Panel Version: 5.286
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.
In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.Created: 12 Apr 2023, 3:37 p.m. | Last Modified: 12 Apr 2023, 3:37 p.m.
Panel Version: 5.37
Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.
In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.Created: 12 Apr 2023, 3:36 p.m. | Last Modified: 12 Apr 2023, 3:36 p.m.
Panel Version: 5.37
Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.
In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.Created: 12 Apr 2023, 3:36 p.m. | Last Modified: 12 Apr 2023, 3:36 p.m.
Panel Version: 5.37
Comment on mode of inheritance: There is sufficient evidence (>3 female cases with monoallelic variants causing ID) to suggest that MOI should be updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' in the next major review.
In addition, intellectual disability (MIM #309530) has been associated in both OMIM and Gene2Phenotype with X-linked dominant inheritance.Created: 12 Apr 2023, 3:35 p.m. | Last Modified: 12 Apr 2023, 3:35 p.m.
Panel Version: 5.36
There are more than 20 unrelated cases identified with variants in IQSEC2 gene, as reported in publications. Moderate to severe intellectual disability was present in all affected males.
De novo, truncating variants correlate with severe disease in both female and male patients harboring an IQSEC2 alteration. Missense variants in male and female patients account for a milder disease overall, with more severe symptoms in males than females.Created: 12 Apr 2023, 3:26 p.m. | Last Modified: 12 Apr 2023, 3:31 p.m.
Panel Version: 5.35
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Intellectual developmental disorder, X-linked 1, OMIM:309530
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;in_gilissen_2014_known . Main mutation mechanism : All missense/in frameCreated: 27 Jul 2017, 6:53 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; find_uk10k; gilissen_2014_known; sfari_20150206; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; gonzalez_mantilla_2016; GEL_ID_green_20160217; neuro_20160418_strict; All missense/in frame. 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, 12:40 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications
Mode of pathogenicity
Other
Phenotypes for gene: IQSEC2 were changed from Mental retardation, X-linked 1, 309530; non-syndromic X-linked intellectual disability; Rett like phenotype in males; MENTAL RETARDATION X-LINKED TYPE 1 (MRX1) to Intellectual developmental disorder, X-linked 1, OMIM:309530
Tag Q2_23_MOI was removed from gene: IQSEC2.
Source NHS GMS was added to IQSEC2. Mode of inheritance for gene IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Mode of inheritance for gene: IQSEC2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Publications for gene: IQSEC2 were set to 20473311; 23674175; 30842726; 31415821; 33368194
Publications for gene: IQSEC2 were set to
Tag Q2_23_MOI tag was added to gene: IQSEC2.
Source Victorian Clinical Genetics Services was added to IQSEC2.
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
IQSEC2 was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene IQSEC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Model of inheritance for gene IQSEC2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
IQSEC2 was added to Intellectual disabilitypanel. Source: Expert Review
Model of inheritance for gene IQSEC2 was changed to X-LINKED: hemizygous mutation in males, may be caused by monoallelic mutations in females
IQSEC2 was added to Intellectual disabilitypanel. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen
IQSEC2 was added to Intellectual disabilitypanel. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen