Marinesco-Sjögren syndrome is a condition that has a variety of signs and symptoms affecting many tissues. People with Marinesco-Sjögren syndrome have cataracts that usually develop soon after birth or in early childhood. Affected individuals also have muscle weakness and difficulty coordinating movements, mild to moderate intellectual disability, and skeletal abnormalities including short stature and scoliosis. Other features of Marinesco-Sjögren syndrome include strabismus, nystagmus, and impaired speech.
Mutations in the SIL1 gene cause Marinesco-Sjögren syndrome. The SIL1 gene provides instructions for producing a protein located in a cell structure called the endoplasmic reticulum. Among its many functions, the endoplasmic reticulum folds and modifies newly formed proteins so they have the correct 3-dimensional shape. The SIL1 protein plays a role in the process of protein folding.
SIL1 gene mutations result in the production of a protein that has little or no activity. A lack of SIL1 protein is thought to impair protein folding, which could disrupt protein transport and cause proteins to accumulate in the endoplasmic reticulum. This accumulation likely damages and destroys cells in many different tissues, leading to ataxia, myopathy, and the other features of Marinesco-Sjögren syndrome.
Methodology: Sequencing of entire coding region
Purpose: Confirmation of Clinical Diagnosis
ICD-10 Code Q99.8
Test Requisition: Sequencing Requisition
CPT Codes: 81479 Cost: $1350.00
Turn-around-time: 5-6 weeks
1. Anttonen AK, Mahjneh I, Hämäläinen RH, Lagier-Tourenne C, Kopra O, et al. (2005) “The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone”. Nat Genet. 37(12):1309-11.
2. Anttonen AK, Siintola E, Tranebjaerg L, Iwata NK, Bijlsma EK, Meguro H, et al. (2008) “Novel SIL1 mutations and exclusion of functional candidate genes in Marinesco-Sjögren syndrome”. Eur J Hum Genet. 16(8):961-9.
3. Eriguchi M, Mizuta H, Kurohara K, Fujitake J, Kuroda Y. (2008) “Identification of a new homozygous frameshift insertion mutation in the SIL1 gene in 3 Japanese patients with Marinesco-Sjögren syndrome”. J Neurol Sci. 270(1-2):197-200.
4. Mahjneh I, Anttonen AK, Somer M, Paetau A, Lehesjoki AE, Somer H, Udd B. (2006) “Myopathy is a prominent feature in Marinesco-Sjögren syndrome: A muscle computed tomography study”. J Neurol. 253(3):301-6.
5. Senderek J, Krieger M, Stendel C, Bergmann C, Moser M, Breitbach-Faller N, et al. (2005) “Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy”. Nat Genet. 37(12):1312-4.