Abstract
BackgroundMarinesco-Sjögren syndrome (MSS) is an autosomal recessive multisystem disorder characterized by the tetralogy of cerebellar ataxia, congenital cataracts, intellectual disability, and progressive muscle weakness due to myopathy. MSS is extremely rare, and its clinical, pathological, and genetic features are not yet fully understood.MethodsWe conducted a nationwide, questionnaire-based survey on MSS in Japan and carefully reviewed the medical records of 36 patients suspected of having this disease. In addition, pathological examinations of muscles, sequence and haplotype analysis in SIL1 were performed.ResultsThe patients had been examined between the ages of 2 and 52 years. Delayed psychomotor development and cataracts from early childhood were observed in all patients, whereas no life-threatening events were observed. Mutations in SIL1 were identified in 24 of the 27 patients tested, and 43 of the 48 chromosomes possessed the SIL1 c.936dupG (p.Leu313fs) mutation. The haplotype analysis revealed that 31 of the 32 chromosomes (96.9%) with the c.936dupG mutation had the same haplotype.ConclusionsThe results of haplotype analysis suggested the presence of a founder effect. The clinical features of patients without SIL1 mutations were indistinguishable from those with SIL1 mutations, suggesting the genetic heterogeneity of MSS.
Highlights
Marinesco-Sjögren syndrome (MSS; OMIM 248800) is an autosomal recessive multisystem disorder clinically characterized by the tetralogy of cerebellar ataxia, congenital cataracts, intellectual disability, and progressive muscle weakness due to myopathy [1,2,3]
Sequence analysis of SIL1 Frozen muscle or peripheral blood lymphocytes were obtained from 27 of the 36 patients suspected of having MSS, for genetic analysis
Mutation of Leu206, which is highly conserved among species, was predicted to exert a deleterious impact on protein function by the Polymorphism Phenotyping v2 (PolyPhen-2; http:// genetics.bwh.harvard.edu/pph2/) and the Sorting Intolerant From Tolerant software (SIFT: http://sift.bii.a-star.edu. sg/)
Summary
Marinesco-Sjögren syndrome (MSS) is an autosomal recessive multisystem disorder characterized by the tetralogy of cerebellar ataxia, congenital cataracts, intellectual disability, and progressive muscle weakness due to myopathy. MSS is extremely rare, and its clinical, pathological, and genetic features are not yet fully understood. Marinesco-Sjögren syndrome (MSS; OMIM 248800) is an autosomal recessive multisystem disorder clinically characterized by the tetralogy of cerebellar ataxia, congenital cataracts, intellectual disability, and progressive muscle weakness due to myopathy [1,2,3]. Bip is an HSP70 chaperone family member located in the ER, and plays a MSS is an extremely rare disease, and very few cases have been reported. We performed a nationwide, questionnaire-based survey on MSS with the aim of characterizing its prevalence, clinical features, natural history, muscle pathological findings, and mutation status
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