A homozygous double mutation in SMN1: a complicated genetic diagnosis of SMA.
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 complexity of SMN mutations and suggests additional testing (gene sequencing) may be appropriate when based on family lines.
Molecular Diagnostics Laboratory, Nemours/Alfred I. duPont Hospital for Children Wilmington, Delaware, 19803.
Susan M
SM
Kirwin
Molecular Diagnostics Laboratory, Nemours/Alfred I. duPont Hospital for Children Wilmington, Delaware, 19803.
Kathy M B
KM
Vinette
Molecular Diagnostics Laboratory, Nemours/Alfred I. duPont Hospital for Children Wilmington, Delaware, 19803.
Iris L
IL
Gonzalez
Dhahran Health Center Dhahran, Saudi Arabia.
Hind Al
HA
Abdulwahed
Dhahran Health Center Dhahran, Saudi Arabia.
Nouriya
N
Al-Sannaa
Molecular Diagnostics Laboratory, Nemours/Alfred I. duPont Hospital for Children Wilmington, Delaware, 19803.
Vicky L
VL
Funanage
Capillary electrophoresis; SMN mutations; SMN1; duplication; spinal muscular atrophy