Intellectual disability - microarray and sequencing
Gene: RELN
Comment on mode of inheritance: The MOI should be updated from "BIALLELIC, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review as there are three unrelated cases with monoallelic RELN variants and intellectual disability reported in the literature.Created: 10 Jan 2024, 12:07 p.m. | Last Modified: 10 Jan 2024, 12:08 p.m.
Panel Version: 5.395
In addition to previously reported cases, PMID:35769015 reported four families with biallelic RELN variants and neurodevelopmental disorder, of which one patient had global developmental delay and patients from another unrelated family had severe intellectual disability.
PMID:35769015 also reported seven unrelated families with monoallelic RELN variants and neurodevelopmental disorder, of which patients from three families had mild-severe intellectual disability.
Biallelic variants have been associated with Lissencephaly 2 in both OMIM (MIM #257320) and Gene2Phenotype (with 'definitive' rating in the DD panel), and impaired intellectual development has been associated as one of the clinical presentations in OMIM. Monoallelic variants have been associated with "{Epilepsy, familial temporal lobe, 7}" (MIM # 616436) in OMIM, which does not currently record ID as one of the clinical presentations.Created: 10 Jan 2024, 12:03 p.m. | Last Modified: 10 Jan 2024, 12:03 p.m.
Panel Version: 5.391
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Publications
Multiple individuals with monoallelic and biallelic variants with different phenotypes are reported: 35769015. Monoallelic variants are mainly missense. The inheritance should be changed to both.Created: 30 Sep 2022, 6:04 p.m. | Last Modified: 30 Sep 2022, 6:04 p.m.
Panel Version: 3.1732
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
Lisencephaly, seizures, autism
Publications
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
LISSENCEPHALY 2
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, 8:14 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_candidate; sfari_20150206; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; gonzalez_mantilla_2016; 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, 1:16 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Mode of inheritance for gene: RELN was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Tag Q4_23_MOI tag was added to gene: RELN.
Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Phenotypes for gene: RELN were changed from Lissencephaly 2 (Norman-Roberts type), 257320; LISSENCEPHALY 2 to Lissencephaly 2 (Norman-Roberts type), OMIM:257320; neurodevelopmental disorder, MONDO:0700092
Publications for gene: RELN were set to
Source Victorian Clinical Genetics Services was added to RELN.
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
RELN was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene RELN was set to BIALLELIC, autosomal or pseudoautosomal
RELN was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen