A nationwide survey on Marinesco-Sjögren syndrome in Japan

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.

BiP and Its Nucleotide Exchange Factors Grp170 and Sil1: Mechanisms of Action and Biological Functions

“…However, three MSS-associated mutations have been identified that disrupt only the last 4 or 5 amino acids of Sil1, which affects its solubility and stability resulting in significantly diminished expression of these Sil1 mutants 98; 99 . Five additional MSS-associated mutations have been identified that result in single amino acid substitutions in Sil1 98; 154; 155; 157; 159; 160 , although the effects of these mutations on Sil1 function or expression have not been examined. It remains unclear why only some tissues appear to be affected by mutations in the ubiquitously expressed Sil1 protein, and in most cases the molecular mechanism(s) underlying the pathology remains unknown.…”

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

“…Somatic findings: Congenital cataract, cerebellar ataxia, mild to moderate developmental delay, short stature, hypergonadotropic hypogonadism, and progressive muscular weakness and muscle atrophy . Peripheral neuropathy, seizures, hearing loss, and acute rhabdomyolysis possible …”

“…CNS: Cerebellar atrophy with/without T2‐hyperintense signal of the cerebellar cortex is common, but not consistent and is most likely due to loss of Purkinje cells and secondary gliosis . Absence or hypoplasia of the pituitary gland and callosal dysgenesis are rare …”

“…Somatic findings: Congenital cataract, cerebellar ataxia, mild to moderate developmental delay, short stature, hypergonadotropic hypogonadism, and progressive muscular weakness and muscle atrophy. 288,289 Peripheral neuropathy, seizures, hearing loss, and acute rhabdomyolysis possible. 288 Skeleton: Microcephaly, short stature, kyphoscoliosis, pes planovalgus, short metatarsals and metacarpals, coxa valga, genu and cubitus valgus, and pectus deformities.…”

Characterization of Zebrafish Models of Marinesco-Sjögren Syndrome

“…Marinesco-Sjögren syndrome (MSS; OMIM 248800) is an autosomal recessive disorder clinically characterized by cerebellar ataxia, mental retardation, congenital cataracts, and progressive muscle weakness [1–4]. Mutations in SIL1 (Gene ID: 64374) were reported to be causative for MSS [5, 6].…”