Abstract:

BACKGROUND: 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.
METHODS: We 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.
RESULTS: The 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.
CONCLUSIONS: The 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.

日本語要旨:

マリネスコ‐シェーグレン症候群は小脳性運動失調、先天性白内障、知能障害、進行性筋力低下を四徴候とする常染色体劣性遺伝性の極めて稀な疾患である。我々は本邦における当疾患の患者において創始者効果がみられる事、SIL1遺伝子異常を伴う患者と伴わない患者では臨床症状に差異がみられず遺伝的多様性がある事を明らかにした。