A new mutation in the skeletal ryanodine receptor gene (RYR1) is potentially causative of malignant hyperthermia, central core disease, and severe skeletal malformation

American Journal of Medical Genetics, Part A - Tập 124A Số 3 - Trang 248-254 - 2004
Henrik Rueffert1, D Olthoff1, C. Deutrich1, R. Schober2, Ursula G. Froster3
1Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, Germany
2Department of Neuropathology, University of Leipzig, Germany
3Institute of Human Genetics, University of Leipzig, Germany

Tóm tắt

AbstractMalignant hyperthermia susceptibility (MHS) and central core disease (CCD) have been shown to result from missense mutations in the ryanodine receptor gene of the skeletal muscle (RYR1). A 15‐year‐old patient who had spondylocostal dysostosis (SCD) developed an MH crisis during general anesthesia. The patient was characterized phenotypically by block vertebrae, vertebral fusion, short neck and thorax, fused ribs, craniofacial abnormalities, spina bifida occulta, and a diaphragmatic defect closed surgically in early infancy. The diagnosis MH susceptible (MHS) was confirmed by the in vitro contracture test (IVCT) on a muscle biopsy. Surprisingly, the histopathological investigation revealed the presence of CCD too. Molecular genetic investigation of the RYR1 gene was performed to search for known MH‐related mutations. Cluster regions of the RYR1 gene, in which mutations have already been found, were examined by direct automated sequencing. In addition to the diagnosis MHS and CCD we were able to identify a novel RYR1 mutation in exon 46: 7358ATC > ACC, resulting in an Ile2453Thr substitution. This mutation was also present in the mother, in whom MH disposition and CCD were determined by muscle investigations. We suggest that the newly identified RYR1 mutation is closely associated with MH and CCD. A probable causative role of the RYR1 gene in SCD patients should be assessed by further genetic investigations. © 2003 Wiley‐Liss, Inc.

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Tài liệu tham khảo

Barone V, 1999, Mutation screening of RYR1 gene and identification of two novel mutations in Italian malignant hyperthermia families, J Med Genet, 36, 115

10.1093/bja/60.3.303

10.1038/74307

10.1172/JCI993

10.1136/bmj.1.5848.272

10.1038/380152a0

10.1136/jnnp.28.5.432

10.1093/bja/56.11.1267

10.1002/1531-8249(200011)48:5<745::AID-ANA8>3.0.CO;2-F

10.1002/ana.410070105

10.1016/0888-7543(91)90084-R

10.1007/BF00197703

Jarcho S, 1938, Hereditary malformation of the vertebral bodies, Bull Johns Hopkins Hosp, 62, 216

10.1007/978-1-4613-2079-1_7

Kalow W, 1970, Metabolic error of muscle metabolism, after recovery from malignant hyperthermia, Lancet, 2, 894

10.1016/0888-7543(91)90461-M

10.1073/pnas.96.7.4164

10.1038/343559a0

10.1086/301748

10.1038/343562a0

10.1002/(SICI)1098-1004(200005)15:5<410::AID-HUMU2>3.0.CO;2-D

10.1002/(SICI)1096-8628(19960202)61:4<310::AID-AJMG3>3.0.CO;2-Y

10.1111/j.1399-6576.1997.tb04820.x

10.1006/geno.1996.0238

10.1038/ng0993-51

10.1016/0960-8966(93)90113-X

10.1086/321270

Shuaib A, 1987, Central core disease. Clinical features in 13 patients, J Comp Path, 97, 597

10.1074/jbc.272.42.26332

10.1074/jbc.274.2.693

10.1042/bj3010661

10.1086/302464

10.1093/bja/86.2.283

10.1034/j.1399-0004.2002.620206.x

10.1016/S0143-4160(03)00072-1

10.1038/ng0993-46

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American Journal of Medical Genetics, Part A

Tập 124A Số 3

248-254

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