The most common mutation in FKRP causing limb girdle muscular dystrophy type 2I (LGMD2I) may have occurred only once and is present in Hutterites and other populations.

Authors: Frosk, Patrick  Greenberg, Cheryl R  Tennese, Alysa A P  Lamont, Ryan  Nylen, Edward  Hirst, Cheryl  Frappier, Danielle  Roslin, Nicole M  Zaik, Michaela  Bushby, Kate  Straub, Volker  Zatz, Mayana  de Paula, Flavia  Morgan, Kenneth  Fujiwara, T Mary  Wrogemann, Klaus 
Citation: Frosk P, etal., Hum Mutat. 2005 Jan;25(1):38-44.
Pubmed: (View Article at PubMed) PMID:15580560
DOI: Full-text: DOI:10.1002/humu.20110

Limb girdle muscular dystrophy (LGMD) is common in the Hutterite population of North America. We previously identified a mutation in the TRIM32 gene in chromosome region 9q32, causing LGMD2H in approximately two-thirds of the 60 Hutterite LGMD patients studied to date. A genomewide scan was undertaken in five families who did not show linkage to the LGMD2H locus on chromosome 9. A second LGMD locus, LGMD2I, was identified in chromosome region 19q13.3, and the causative mutation was identified as c.826C>A (L276I), a missense mutation in the FKRP gene. A comparison of the clinical characteristics of the two LGMD patient groups in this population reveals some differences. LGMD2I patients generally have an earlier age at diagnosis, a more severe course, and higher serum creatine kinase (CK) levels. In addition, some of these patients show calf hypertrophy, cardiac symptoms, and severe reactions to general anesthesia. None of these features are present among LGMD2H patients. A single common haplotype surrounding the FKRP gene was identified in the Hutterite LGMD2I patients. An identical core haplotype was also identified in 19 other non-Hutterite LGMD2I patients from Europe, Canada, and Brazil. The occurrence of this mutation on a common core haplotype suggests that L276I is a founder mutation that is dispersed among populations of European origin.

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CRRD ID: 11667967
Created: 2017-01-19
Species: All species
Last Modified: 2017-01-19
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.