LINS1 variants were first reported in connection to autosomal recessive neurodevelopmental disorder in 2011 by a study identifying candidate genes for autosomal recessive intellectual disability (Najmabadi H et al., PMID: 21937992). Common phenotypes for individuals with LINS1 variants include intellectual disability, autistic features, hyperactive behavior, stereotypical movements, and mutism. Additionally, some patients exhibited muscular hypotonia, schizophrenia, anxiety, and features of Worster-Drought syndrome (described as a form of cerebral palsy affecting muscles of the mouth and throat) including drooling, dysphagia, and impaired tongue movement. Given the spectrum of neurodevelopmental features observed, the gene is curated under “complex neurodevelopmental disorder” (http://purl.obolibrary.org/obo/MONDO_0100038). Eight homozygous variants of various types (frameshift (2), nonsense (4), splicing (1), and missense (1)), reported in 15 individuals in seven publications have been included in this curation (PMIDs: 21937992, 23773660, 28181389, 30090841, 32802957, 32499722, 34450347). The presumed mechanism of pathogenicity based on published evidence is loss of function. The maximum score for genetic evidence (12 pts.) has been reached. In summary, there is definitive evidence to support the relationship between LINS1 and autosomal recessive complex neurodevelopmental disorder. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism expert panel on February 7, 2023 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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