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| Intellectual disability - microarray and sequencing v2.652 | LINGO1 | Ivone Leong Classified gene: LINGO1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.652 | LINGO1 | Ivone Leong Added comment: Comment on list classification: Gave LINO1 amber gene rating based on review by Konstantinos Varvagiannis (Other). Have so added the 'watchilist' tag. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.652 | LINGO1 | Ivone Leong Gene: lingo1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.651 | LINGO1 | Ivone Leong Tag watchlist tag was added to gene: LINGO1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.584 | LINGO1 |
Konstantinos Varvagiannis gene: LINGO1 was added gene: LINGO1 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: LINGO1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LINGO1 were set to 28837161 Phenotypes for gene: LINGO1 were set to Mental retardation, autosomal recessive 64 (MIM 618103) Penetrance for gene: LINGO1 were set to Complete Review for gene: LINGO1 was set to AMBER gene: LINGO1 was marked as current diagnostic Added comment: Biallelic pathogenic variants in LINGO1 cause Mental retardation, autosomal recessive 64 (MIM 618103). Ansar et al. (PMID: 28837161) report on 5 individuals from 2 consanguineous Pakistani families. Affected individuals from both families presented with similar phenotype consisting of global developmental delay (5/5), intellectual disability (5/5), microcephaly (4/5) as well as abnormal behavior (5/5). Subjects from both families were homozygous for missense variants (private to each family) affecting proximal residues (290 and 288) of the protein (NM_032808.6:c.869G>A or p.Arg290His and c.863A>G or p.Tyr288Cys). All variants were absent in an ethnically matched control cohort (201 individuals) as well as the relevant subpopulation in gnomAD. Functional studies were not performed. LINGO1 is a transmembrane protein predominantly expressed in the CNS. Previous studies suggest that this protein has an important role in myelination, neuronal survival and CNS repair. LINGO1 is rather intolerant to both missense and LoF variants (Z-score of 4 and pLI of 0.95). According to the authors these variants may be hypomorphic, which might in turn suggest that monoallelic heterozygous LoF mutations could cause ID (although this remains an assumption). This gene is not associated with any phenotype in G2P but is included in panels for ID offered by diagnostic laboratories (incl. Radboudumc). As a result, LINGO1 can be considered for inclusion in this panel probably as amber (2 families, no functional studies). Sources: Literature, Radboud University Medical Center, Nijmegen |
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