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http://purl.uniprot.org/citations/26566883http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26566883http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26566883http://www.w3.org/2000/01/rdf-schema#comment"

Background

Intellectual disability (ID) is a neurodevelopmental disorder affecting 1%-3% of the population worldwide. It is characterised by high phenotypic and genetic heterogeneity and in most cases the underlying cause of the disorder is unknown. In our study we investigated a large consanguineous family from Baluchistan, Pakistan, comprising seven affected individuals with a severe form of autosomal recessive ID (ARID) and epilepsy, to elucidate a putative genetic cause.

Methods and results

Whole exome sequencing (WES) of a trio, including a child with ID and epilepsy and its healthy parents that were part of this large family, revealed a homozygous missense variant p.R53Q in the lectin mannose-binding 2-like (LMAN2L) gene. This homozygous variant was co-segregating in the family with the phenotype of severe ID and infantile epilepsy; unaffected family members were heterozygous variant carriers. The variant was predicted to be pathogenic by five different in silico programmes and further three-dimensional structure modelling of the protein suggests that variant p.R53Q may impair protein-protein interaction. LMAN2L (OMIM: 609552) encodes for the lectin, mannose-binding 2-like protein which is a cargo receptor in the endoplasmic reticulum important for glycoprotein transport. Genome-wide association studies have identified an association of LMAN2L to different neuropsychiatric disorders.

Conclusion

This is the first report linking LMAN2L to a phenotype of severe ARID and seizures, indicating that the deleterious homozygous p.R53Q variant very likely causes the disorder."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.org/dc/terms/identifier"doi:10.1136/jmedgenet-2015-103179"xsd:string
http://purl.uniprot.org/citations/26566883http://purl.org/dc/terms/identifier"doi:10.1136/jmedgenet-2015-103179"xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Wiemann S."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Wiemann S."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Schlesner M."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Schlesner M."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Mustafa G."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Mustafa G."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Rappold G.A."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Rappold G.A."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Wade R.C."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Wade R.C."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Thiel C."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Thiel C."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Aslamkhan M."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Aslamkhan M."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Berkel S."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Berkel S."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Paramasivam N."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Paramasivam N."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Rafiullah R."xsd:string
http://purl.uniprot.org/citations/26566883http://purl.uniprot.org/core/author"Rafiullah R."xsd:string
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