title: 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.
abstract: 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.
authors.affiliation: Department of Biochemistry, University of Manitoba, Winnipeg, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Frosk
authors.forename: Cheryl R
authors.initials: CR
authors.lastname: Greenberg
authors.forename: Alysa A P
authors.initials: AA
authors.lastname: Tennese
authors.forename: Ryan
authors.initials: R
authors.lastname: Lamont
authors.forename: Edward
authors.initials: E
authors.lastname: Nylen
authors.forename: Cheryl
authors.initials: C
authors.lastname: Hirst
authors.forename: Danielle
authors.initials: D
authors.lastname: Frappier
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Roslin
authors.forename: Michaela
authors.initials: M
authors.lastname: Zaik
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
authors.forename: Flavia
authors.initials: F
authors.lastname: de Paula
authors.forename: Kenneth
authors.initials: K
authors.lastname: Morgan
authors.forename: T Mary
authors.initials: TM
authors.lastname: Fujiwara
authors.forename: Klaus
authors.initials: K
authors.lastname: Wrogemann
mesh_terms: D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004252:DNA Mutational Analysis; D018703:Founder Effect; D005838:Genotype; D006801:Humans; D049288:Muscular Dystrophies, Limb-Girdle / Q000208:ethnology* / Q000235:genetics*; D009154:Mutation; D009656:North America; D010430:Pentosyltransferases; D010641:Phenotype; D011506:Proteins / Q000235:genetics*
chemical_list: D011506:Proteins; C443107:FKRP protein, human; D010430:Pentosyltransferases