title: A frameshift mutation of ERLIN2 in recessive intellectual disability, motor dysfunction and multiple joint contractures.
abstract: We present a family afflicted with a novel autosomal recessive disease characterized by progressive intellectual disability, motor dysfunction and multiple joint contractures. No pathology was found by cranial imaging, electromyography and muscle biopsy, but electron microscopy in leukocytes revealed large vacuoles containing flocculent material. We mapped the disease gene by SNP genome scan and linkage analysis to an ∼0.80 cM and 1 Mb region at 8p11.23 with a multipoint logarithm of odds (LOD) score of 12. By candidate gene approach, we identified a homozygous two-nucleotide insertion in ERLIN2, predicted to lead to the truncation of the protein by about 20%. The gene encodes endoplasmic reticulum (ER) lipid raft-associated protein 2 that mediates the ER-associated degradation of activated inositol 1,4,5-trisphosphate receptors and other substrates.
authors.affiliation: Department of Molecular Biology and Genetics, Boğaziçi University, Istanbul 34342, Turkey.
authors.forename: Yeşerin
authors.initials: Y
authors.lastname: Yıldırım
authors.forename: Elif Kocasoy
authors.initials: EK
authors.lastname: Orhan
authors.forename: Sibel Aylin Ugur
authors.initials: SA
authors.lastname: Iseri
authors.forename: Piraye
authors.initials: P
authors.lastname: Serdaroglu-Oflazer
authors.forename: Bülent
authors.initials: B
authors.lastname: Kara
authors.forename: Seyhun
authors.initials: S
authors.lastname: Solakoğlu
authors.forename: Aslıhan
authors.initials: A
authors.lastname: Tolun
mesh_terms: D000293:Adolescent; D001176:Arthrogryposis / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003241:Consanguinity; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D023061:Gene Order; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome; D055815:Young Adult
chemical_list: C121703:ERLIN2 protein, human; D008565:Membrane Proteins