FKRP gene mutations cause congenital muscular dystrophy, mental retardation, and cerebellar cysts

被引:93
作者
Topaloglu, H
Brockington, M
Yuva, Y
Talim, B
Haliloglu, G
Blake, D
Torelli, S
Brown, SC
Muntoni, F
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Pediat, Dubowitz Neuromuscular Ctr, London W12 0NN, England
[2] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England
[3] Hacettepe Univ, Dept Pediat Neurol, TR-06100 Ankara, Turkey
[4] Hacettepe Univ, Dept Pediat Pathol, TR-06100 Ankara, Turkey
关键词
D O I
10.1212/01.WNL.0000052996.14099.DC
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Congenital muscular dystrophies (CMD) are autosomal recessive disorders that present within the first 6 months of life with hypotonia and a dystrophic muscle biopsy. CNS involvement is present in some forms. The fukutin-related protein gene (FKRP) is mutated in a severe form of CMD (MDC1C) and a milder limb girdle dystrophy (LGMD2I). Both forms have secondary deficiencies of laminin alpha2 and alpha-dystroglycan immunostaining. Structural brain involvement has not been observed in patients with FKRP gene mutations. Methods: The authors studied two tin elated patients who had a pattern of muscle involvement identical to MDC1C, mental retardation, and cerebellar cysts on cranial MRI. The FKRP gene was analyzed along with the skeletal muscle expression of laminin alpha2 and alpha-dystroglycan. Results: The muscle biopsy of both patients showed severe dystrophic findings, a reduction in laminin alpha2, and profound depletion of alpha-dystroglycan. Both patients had homozygous FKRP gene mutations not previously reported (C663A [Ser221Arg] and C981A [Pro315Thr]). Conclusions: Mutations within the FKRP gene can result in CMD associated with mental retardation and cerebellar cysts. This adds structural brain defects to the already wide spectrum of abnormalities caused by FKRP mutations. The severe depletion of alpha-dystroglycan expression suggests that FKRP is involved in the processing of alpha-dystroglyean.
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页码:988 / 992
页数:5
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