A homozygous double mutation in SMN1: a complicated genetic diagnosis of SMA.

ABSTRACT: Spinal muscular atrophy (SMA), the most common autosomal recessive cause of infant death, is typically diagnosed by determination of SMN1 copy number. Approximately 3-5% of patients with SMA retain at least one copy of the SMN1 gene carrying pathogenic insertions, deletions, or point mutations. We report a patient with SMA who is homozygous for two mutations carried in cis: an 8 bp duplication (c.48_55dupGGATTCCG; p.Val19fs*24) and a point mutation (c.662C>T; p.Pro221Leu). The consanguineous parents carry the same two mutations within one SMN1 gene copy. We demonstrate that a more accurate diagnosis of the disease is obtained through a novel diagnostic assay and development of a capillary electrophoresis method to determine the copy number of their mutant alleles. This illustrates the comp

SUBMITTER: Kirwin SM 

PROVIDER: S-EPMC3865576 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature