Phenotypic spectrum associated with mutations in the fukutin-related protein gene.
We describe 22 patients with mutations in the fukutin-related protein (FKPR) gene. Four patients had congenital muscular dystrophy (MDC1C), with presentation at birth, severe weakness and inability to stand unsupported. The other 18 had limb girdle muscular dystrophy (LGMD2I). Eleven showed a Duchenne-like course with loss of ambulation in the early teens while 7 had a milder phenotype. Muscle biopsy invariably showed abnormal expression of a-dystroglycan. MDC1C patients either carried 2 missense or 1 missense and 1 nonsense mutations. Patients with LGMD2I shared a common mutation (C826A,Leu276Ileu) and their phenotypic severity was correlated with the second allelic mutation.
Mercuri
Eugenio
E
Dubowitz Neuromuscular Centre, Department of Paediatrics, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom. e.mercuri@ic.ac.uk
Brockington
Martin
M
Straub
Volker
V
Quijano-Roy
Susana
S
Yuva
Yeliz
Y
Herrmann
Ralf
R
Brown
Susan C
SC
Torelli
Silvia
S
Dubowitz
Victor
V
Blake
Derek J
DJ
Romero
Norma B
NB
Estournet
Brigitte
B
Sewry
Caroline A
CA
Guicheney
Pascale
P
Voit
Thomas
T
Muntoni
Francesco
F
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001706:Biopsy; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics; D049030:Dystroglycans; D005260:Female; D006801:Humans; D007040:Hypoventilation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000473:pathology; D020125:Mutation, Missense; D010430:Pentosyltransferases; D017933:Peripheral Nervous System / Q000473:pathology; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D018487:Ventricular Dysfunction, Left / Q000235:genetics
D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D008562:Membrane Glycoproteins; D011506:Proteins; D049030:Dystroglycans; C443107:FKRP protein, human; D010430:Pentosyltransferases