Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations.
Merosin deficient congenital muscular dystrophy 1A (MDC1A) results from mutations in the LAMA2 gene. We report 51 patients with MDC1A and examine the relationship between degree of merosin expression, genotype and clinical features. Thirty-three patients had absence of merosin and 13 showed some residual merosin. Compared to the residual merosin group, patients with absent merosin had an earlier presentation (<7days) (P=0.0073), were more likely to lack independent ambulation (P=0.0215), or require enteral feeding (P=0.0099) and ventilatory support (P=0.0354). We identified 33 novel LAMA2 mutations; these were distributed throughout the gene in patients with absent merosin, with minor clusters in exon 27, 14, 25 and 26 (55% of mutations). Patients with residual merosin often carried at least one splice site mutation and less frequently frameshift mutations. This large study identified novel LAMA2 mutations and highlights the role of immunohistochemical studies for merosin status in predicting clinical severity of MDC1A.
Geranmayeh
Fatemeh
F
Dubowitz Neuromuscular Centre, Institute of Child Health & Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, United Kingdom.
Clement
Emma
E
Feng
Lucy H
LH
Sewry
Caroline
C
Pagan
Judith
J
Mein
Rachael
R
Abbs
Stephen
S
Brueton
Louise
L
Childs
Anne-Marie
AM
Jungbluth
Heinz
H
De Goede
Christian G
CG
Lynch
Bryan
B
Lin
Jean-Pierre
JP
Chow
Gabriel
G
Sousa
Carlos de
Cd
O'Mahony
Olivia
O
Majumdar
Anirban
A
Straub
Volker
V
Bushby
Katherine
K
Muntoni
Francesco
F
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D051346:Mobility Limitation; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics; D012133:Respiratory Paralysis; D055815:Young Adult
D007797:Laminin; D022821:RNA Splice Sites; C102645:laminin alpha 2