Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations.

Hdl Handle:
http://hdl.handle.net/10147/200275
Title:
Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations.
Authors:
Geranmayeh, Fatemeh; Clement, Emma; Feng, Lucy H; Sewry, Caroline; Pagan, Judith; Mein, Rachael; Abbs, Stephen; Brueton, Louise; Childs, Anne-Marie; Jungbluth, Heinz; De Goede, Christian G; Lynch, Bryan; Lin, Jean-Pierre; Chow, Gabriel; Sousa, Carlos de; O'Mahony, Olivia; Majumdar, Anirban; Straub, Volker; Bushby, Katherine; Muntoni, Francesco
Affiliation:
Dubowitz Neuromuscular Centre, Institute of Child Health & Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, United Kingdom.
Citation:
Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations. 2010, 20 (4):241-50 Neuromuscul. Disord.
Publisher:
Elsevier
Journal:
Neuromuscular disorders : NMD
Issue Date:
Apr-2010
URI:
http://hdl.handle.net/10147/200275
DOI:
10.1016/j.nmd.2010.02.001
PubMed ID:
20207543
Abstract:
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.
Item Type:
Article
Language:
en
MeSH:
Adolescent; Child; Child, Preschool; DNA Mutational Analysis; Disease Progression; Exons; Frameshift Mutation; Genetic Testing; Genotype; Humans; Immunohistochemistry; Infant; Laminin; Mobility Limitation; Muscular Dystrophies; Mutation; Phenotype; RNA Splice Sites; Respiratory Paralysis; Young Adult
ISSN:
1873-2364

Full metadata record

DC FieldValue Language
dc.contributor.authorGeranmayeh, Fatemehen
dc.contributor.authorClement, Emmaen
dc.contributor.authorFeng, Lucy Hen
dc.contributor.authorSewry, Carolineen
dc.contributor.authorPagan, Judithen
dc.contributor.authorMein, Rachaelen
dc.contributor.authorAbbs, Stephenen
dc.contributor.authorBrueton, Louiseen
dc.contributor.authorChilds, Anne-Marieen
dc.contributor.authorJungbluth, Heinzen
dc.contributor.authorDe Goede, Christian Gen
dc.contributor.authorLynch, Bryanen
dc.contributor.authorLin, Jean-Pierreen
dc.contributor.authorChow, Gabrielen
dc.contributor.authorSousa, Carlos deen
dc.contributor.authorO'Mahony, Oliviaen
dc.contributor.authorMajumdar, Anirbanen
dc.contributor.authorStraub, Volkeren
dc.contributor.authorBushby, Katherineen
dc.contributor.authorMuntoni, Francescoen
dc.date.accessioned2012-01-05T14:13:02Z-
dc.date.available2012-01-05T14:13:02Z-
dc.date.issued2010-04-
dc.identifier.citationGenotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations. 2010, 20 (4):241-50 Neuromuscul. Disord.en
dc.identifier.issn1873-2364-
dc.identifier.pmid20207543-
dc.identifier.doi10.1016/j.nmd.2010.02.001-
dc.identifier.urihttp://hdl.handle.net/10147/200275-
dc.description.abstractMerosin 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.-
dc.language.isoenen
dc.publisherElsevieren
dc.subject.meshAdolescent-
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshDNA Mutational Analysis-
dc.subject.meshDisease Progression-
dc.subject.meshExons-
dc.subject.meshFrameshift Mutation-
dc.subject.meshGenetic Testing-
dc.subject.meshGenotype-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshInfant-
dc.subject.meshLaminin-
dc.subject.meshMobility Limitation-
dc.subject.meshMuscular Dystrophies-
dc.subject.meshMutation-
dc.subject.meshPhenotype-
dc.subject.meshRNA Splice Sites-
dc.subject.meshRespiratory Paralysis-
dc.subject.meshYoung Adult-
dc.titleGenotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations.en
dc.typeArticleen
dc.contributor.departmentDubowitz Neuromuscular Centre, Institute of Child Health & Great Ormond Street Hospital, 30 Guilford Street, London WC1N 1EH, United Kingdom.en
dc.identifier.journalNeuromuscular disorders : NMDen
dc.description.provinceMunster-

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