These authors contributed equally to this work.
LAMA2 gene analysis in a cohort of 26 congenital muscular dystrophy patients
Version of Record online: 12 AUG 2008
© 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard
Volume 74, Issue 6, pages 502–512, December 2008
How to Cite
Oliveira, J., Santos, R., Soares-Silva, I., Jorge, P., Vieira, E., Oliveira, M., Moreira, A., Coelho, T., Ferreira, J., Fonseca, M., Barbosa, C., Prats, J., Aríztegui, M., Martins, M., Moreno, T., Heinimann, K., Barbot, C., Pascual-Pascual, S., Cabral, A., Fineza, I., Santos, M. and Bronze-da-Rocha, E. (2008), LAMA2 gene analysis in a cohort of 26 congenital muscular dystrophy patients. Clinical Genetics, 74: 502–512. doi: 10.1111/j.1399-0004.2008.01068.x
- Issue online: 20 NOV 2008
- Version of Record online: 12 AUG 2008
- Received 14 April 2008, revised and accepted for publication 12 June 2008
- congenital muscular dystrophy;
- gross deletion;
Congenital muscular dystrophy type 1A (MDC1A) is caused by mutations in the LAMA2 gene encoding laminin-α2. We describe the molecular study of 26 patients with clinical presentation, magnetic resonance imaging and/or laminin-α2 expression in muscle, compatible with MDC1A. The combination of full genomic sequencing and complementary DNA analysis led to the particularly high mutation detection rate of 96% (50/52 disease alleles). Besides 22 undocumented polymorphisms, 18 different mutations were identified in the course of this work, 14 of which were novel. In particular, we describe the first fully characterized gross deletion in the LAMA2 gene, encompassing exon 56 (c.7750-1713_7899-2153del), detected in 31% of the patients. The only two missense mutations detected were found in heterozygosity with nonsense or truncating mutations in the two patients with the milder clinical presentation and a partial reduction in muscle laminin-α2. Our results corroborate the previous few genotype/phenotype correlations in MDC1A and illustrate the importance of screening for gross rearrangements in the LAMA2 gene, which may be underestimated in the literature.