A homozygous double mutation in SMN1: a complicated genetic diagnosis of SMA. Issue 2 (30th May 2013)

• Record Type: Journal Article
• Authors: Kirwin, Susan M.; Vinette, Kathy M. B.; Gonzalez, Iris L.; Abdulwahed, Hind Al; Al‐Sannaa, Nouriya; Funanage, Vicky L.
• Is Part Of: Molecular genetics & genomic medicine. Volume 1:Issue 2(2013:Jul.)
• Page Start: 113
• Page End: 117
• Publication Date: 2013-05-30
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.10
• Languages: English
• ISSNs: 2324-9269

Abstract

<abstract abstract-type="main" id="mgg310-abs-0001"> <title>Abstract</title> <p>Spinal muscular atrophy (SMA), the most common autosomal recessive cause of infant death, is typically diagnosed by determination of <italic>SMN1</italic> copy number. Approximately 3–5% of patients with SMA retain at least one copy of the <italic>SMN1</italic> gene carrying pathogenic insertions, deletions, or point mutations. We report a patient with SMA who is homozygous for two mutations carried <italic>in cis</italic>: an 8 bp duplication (c.48_55dupGGATTCCG; p.Val19fs*24) and a point mutation (c.662C&gt;T; p.Pro221Leu). The consanguineous parents carry the same two mutations within one <italic>SMN1</italic> 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 complexity of <italic>SMN</italic> mutations and suggests additional testing (gene sequencing) may be appropriate when based on family lines.</p> </abstract>