[Hot spot mutation screening of RYR1 gene in diagnosis of congenital myopathies].

Abstract

OBJECTIVE:

To detect hot spot mutation of RYR1 gene in 15 cases of congenital myopathy with different subtypes, and to discuss the value of RYR1 gene hot spot mutation detection in the diagnosis of the disease.

METHODS:

Clinical data were collected in all the patients, including clinical manifestations and signs, serum creatine kinase, electromyography. Fourteen of the patients accepted the muscle biopsy. Hot spot mutation in the C-terminal of RYR1 gene (extron 96-106) had been detected in all the 15 patients.

RESULTS:

All the patients presented with motor development delay, and they could walk at the age of 1 to 3.5 years,but were always easy to fall and could not run or jump. There were no progressive deteriorations. Physical examination showed different degrees of muscle weakness and hypotonia.High arched palates were noted in 3 patients. The serum levels of creatine kinase were mildly elevated in 3 cases, and normal in 12 cases. Electromyography showed "myogenic" features in 11 patients, being normal in the other 4 patients. Muscle biopsy pathologic diagnosis was the central core disease in 3 patients, the central nuclei in 2 patients, the congenital fiber type disproportion in 2 patients, the nameline myopathy in 3 patient, the multiminicore disease in 1 patient, and nonspecific minimal changes in the other 3 patients; one patient was diagnosed with central core disease according to positive family history and gene mutation. In the family case (Patient 2) of central core disease, the c.14678G>A (p.Arg4893Gln) mutation in 102 extron of RYR1 was identified in three members of the family, which had been reported to be a pathogenic mutation. The c.14596A>G(p.Lys4866Gln) mutation in 101 extron was found in one patient with central core disease(Patient 1), and the c.14719G>A(p.Gly4907Ser) mutation in 102 extron was found in another case of the central core disease(Patient 3).The same novel mutation was verified in one of the patients' (Patient 3) asymptomatic father.

CONCLUSION:

Congenital myopathies in the different subtype have the similar clinical manifestations, signs, enzyme detection and electromyography changes. Muscle biopsy plays an important role in the selection of genes to be detected. Hot spot mutation in C-terminal of the RYR1 gene can only be identified in patients with central core disease, so we suggest this hot spot gene mutation screening apply to the suspicious patient with central core disease only.

• Authors: Xing-zhi Chang, Yi-wen Jin, Jing-min Wang, Yun Yuan, Hui Xiong, Shuang Wang, Jiong Qin
• Journal: Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences (Beijing Da Xue Xue Bao Yi Xue Ban) Vol. 46 Issue 5 Pg. 691-7 (Oct 18 2014) ISSN: 1671-167X [Print] China
• PMID: 25331388 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ryanodine Receptor Calcium Release Channel

Topics

• Biopsy
• DNA Mutational Analysis
• Electromyography
• Humans
• Mutation
• Myopathies, Structural, Congenital (genetics)
• Myopathy, Central Core (genetics)
• Pedigree
• Ryanodine Receptor Calcium Release Channel (genetics)