Document Detail

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.
MedLine Citation:
PMID:  15580560     Owner:  NLM     Status:  MEDLINE    
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.
Patrick Frosk; Cheryl R Greenberg; Alysa A P Tennese; Ryan Lamont; Edward Nylen; Cheryl Hirst; Danielle Frappier; Nicole M Roslin; Michaela Zaik; Kate Bushby; Volker Straub; Mayana Zatz; Flavia de Paula; Kenneth Morgan; T Mary Fujiwara; Klaus Wrogemann
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human mutation     Volume:  25     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-22     Completed Date:  2006-02-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  38-44     Citation Subset:  IM    
Copyright Information:
(c) 2004 Wiley-Liss, Inc.
Department of Biochemistry, University of Manitoba, Winnipeg, Canada.
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MeSH Terms
Chromosome Mapping
Chromosomes, Human, Pair 19
DNA Mutational Analysis
Founder Effect
Muscular Dystrophies, Limb-Girdle / ethnology*,  genetics*
North America
Proteins / genetics*
Reg. No./Substance:
0/FKRP protein, human; 0/Proteins

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