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Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation.

Authors: Harel, Tamar  Goldberg, Yael  Shalev, Stavit A  Chervinski, Ilana  Ofir, Rivka  Birk, Ohad S 
Citation: Harel T, etal., Eur J Hum Genet. 2004 Jan;12(1):38-43.
Pubmed: (View Article at PubMed) PMID:14523375
DOI: Full-text: DOI:10.1038/sj.ejhg.5201087

Limb-girdle muscular dystrophies (LGMDs) represent a group of diseases characterized mainly by muscle wasting of the upper and lower limbs, with a wide range of clinical severity. The clinical heterogeneity is paralleled by molecular heterogeneity; each of the 10 forms of autosomal-recessive LGMD recognized to date is caused by mutations in a distinct gene. In a large consanguineous Bedouin tribe living in northern Israel, 15 individuals affected by LGMD demonstrate an autosomal recessive pattern of inheritance. A genome-wide screen followed by fine mapping in this family revealed linkage to a region on chromosome 19 harboring the fukutin-related protein gene (FKRP), with a maximal LOD score of 4.8 for D19S902. FKRP, encoding a putative glycosyltransferase, has been implicated in causing congenital muscular dystrophy 1C (MDC1C), and has recently been shown to be mutated in LGMD2I. We identified a novel missense mutation in exon 4 of the FKRP gene in all the patients studied. Although all affected individuals were homozygous for the same mutation, a marked phenotypic variability was apparent within the family. This finding may suggest a role of modifier genes and environmental factors in LGMD2I. Moreover, the demonstration that an identical, novel mutation in the FKRP gene can cause a muscle disease of either a congenital onset or of a later onset within a single family provides clinical support to the molecular evidence, suggesting that MDC1C and LGMD2I are overlapping ends of one and the same entity.

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RGD Object Information
RGD ID: 11667959
Created: 2017-01-19
Species: All species
Last Modified: 2017-01-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.