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Online mutation report
FKRP (826C>A) frequently causes limb-girdle muscular dystrophy in German patients
  1. M C Walter1,
  2. J A Petersen1,
  3. R Stucka1,
  4. D Fischer2,
  5. R Schröder2,
  6. M Vorgerd3,
  7. A Schroers3,
  8. H Schreiber4,
  9. C O Hanemann4,
  10. U Knirsch4,
  11. A Rosenbohm4,
  12. A Huebner5,
  13. N Barisic6,
  14. R Horvath7,
  15. S Komoly7,
  16. P Reilich1,
  17. W Müller-Felber1,
  18. D Pongratz1,
  19. J S Müller1,
  20. E A Auerswald1,
  21. H Lochmüller1
  1. 1Gene Center, Friedrich-Baur-Institute, and Department of Neurology, Ludwig-Maximilians-University of Munich, Germany
  2. 2Department of Neurology, University of Bonn, Germany
  3. 3Department of Neurology, Ruhr-University of Bochum, Germany
  4. 4Department of Neurology, University of Ulm, Germany
  5. 5Department of Pediatrics, Technical University of Dresden, Germany
  6. 6Department of Pediatrics, Zagreb Medical School, Zagreb, Croatia
  7. 7Department of Neurology, Jahn Ferenc Teaching Hospital, Budapest, Hungary
  1. Correspondence to:
 H Lochmüller
 Gene Center, Ludwig-Maximilians-University, Feodor-Lynen-Str. 25, 81377 Munich, Germany; hannslmb.uni-muenchen.de

https://doi.org/10.1136/jmg.2003.013953

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    Limb-girdle muscular dystrophies (LGMD) and congenital muscular dystrophies (MDC) represent two heterogeneous groups of genetic diseases differing in clinical severity and age of onset.1–6 Mutations in the LAMA2 gene can result in either MDC or, more rarely, LGMD.7 Laminin α2 forms a link between α-dystroglycan and the basal lamina. α-Dystroglycan is a heavily glycosylated peripheral membrane component of the dystrophin-associated-glycoprotein complex (DAG), whilst β-dystroglycan, derived from the same gene, is a transmembrane protein that links to dystrophin intracellularly. Dystroglycan therefore plays a pivotal role in linking the actin-associated cytoskeleton to components of the extracellular matrix, and disruption of this axis is associated with several forms of muscular dystrophy.8 Recently, abnormalities of α-dystroglycan glycosylation have been reported for several forms of MDC and for LGMD2I. A novel gene encoding a putative glycosyltransferase, fukutin-related protein (FKRP), was found to be responsible for both a novel form of MDC (MDC1C) and for LGMD2I.1–5 Interestingly, the single homozygous point mutation (826C>A) leading to an amino acid exchange (Leu276Ile) is associated with a relatively benign clinical phenotype,9,10 whereas patients compound heterozygous for the 826C>A mutation may show a more severe clinical phenotype. We investigated the frequency of the FKRP mutation (826C>A) in 124 LGMD patients and correlated these findings with the clinical phenotype.

    METHODS

    Patients

    All patients described in this study were examined by one of the coauthors. Most patients described are of German descent and reside in Germany. One patient is Croatian (patient 2 in the table), and one patient (patient 19 in the table) is of German descent, but lives in Hungary.

    Consanguinity was not reported. Pedigrees were compatible with autosomal recessive traits. Electromyography of affected muscles in all patients was compatible with chronic myopathy. The clinical findings of all patients are summarised in the table. Diagnostic …

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    Footnotes

    • JSM receives a scholarship from the Boehringer Ingelheim Fonds. This work was supported in part by grants from the Deutsche Forschungsgemeinschaft and the Duchenne Parents Project of Germany (aktion benni & co) to HL. MCW, MV, RS, HS, AH, WMF, DP, and HL are members of the German network on muscular dystrophies (MD-NET, grant number 01GM0302) funded by the German ministry of education and research (BMBF, Bonn, Germany).

    • Conflict of interest: none declared.

    • M C Walter and J Petersen contributed equally to this paper.