Genetic syndrome associating cerebellar ataxia, congenital cataracts, and retarded somatic and mental maturation.

Clinical synopsis

 cerebellar ataxia
 congenital cataract
 retarded somatic maturation
 retarded mental maturation

Microscopical synopsis

 massive cerebellar cortical atrophy with vacuolated or binucleated Purkinje cells
 myopathic changes on muscle biopsy
 numerous enlarged lysosomes containing whorled lamellar or amorphous inclusion bodies by electron microscopy

Etiology

 germline mutations of the SIL1 gene (MIM.608005)

• loss-of-function mutations in SIL1 (#16282978#)
• SIL1 encodes a nucleotide exchange factor for the heat-shock protein 70 (HSP70) chaperone HSPA5.
• SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP (also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum.
   disturbed SIL1-HSPA5 interaction and protein folding is the primary pathology in Marinesco-Sjogren syndrome.

 germline mutations of SARA2 gene in association of Marinesco-Sjogren syndrome and chylomicron retention syndrome (CMRD)

References

 Anttonen AK, Mahjneh I, Hamalainen RH, Lagier-Tourenne C, Kopra O, Waris L, Anttonen M, Joensuu T, Kalimo H, Paetau A, Tranebjaerg L, Chaigne D, Koenig M, Eeg-Olofsson O, Udd B, Somer M, Somer H, Lehesjoki AE. The gene disrupted in Marinesco-Sjogren syndrome encodes SIL1, an HSPA5 cochaperone. Nat Genet. 2005 Dec;37(12):1309-11. PMID: #16282978#

 Senderek J, Krieger M, Stendel C, Bergmann C, Moser M, Breitbach-Faller N, Rudnik-Schoneborn S, Blaschek A, Wolf NI, Harting I, North K, Smith J, Muntoni F, Brockington M, Quijano-Roy S, Renault F, Herrmann R, Hendershot LM, Schroder JM, Lochmuller H, Topaloglu H, Voit T, Weis J, Ebinger F, Zerres K. Mutations in SIL1 cause Marinesco-Sjogren syndrome, a cerebellar ataxia with cataract and myopathy. Nat Genet. 2005 Dec;37(12):1312-4. PMID: #16282977#