Genotype-Phenotype Correlation of SMN1 and NAIP Deletions in Korean Patients with Spinal Muscular Atrophy.
- Author:
Eun Ji AHN
1
;
Mi Sun YUM
;
Eun Hee KIM
;
Han Wook YOO
;
Beom Hee LEE
;
Gu Hwan KIM
;
Tae Sung KO
Author Information
- Publication Type:Original Article
- Keywords: spinal muscular atrophy; SMN1; NAIP; genotype; phenotype
- MeSH: Atrophy; Chungcheongnam-do; Exons; Genetic Association Studies*; Genotype; Humans; Male; Motor Neurons; Multiplex Polymerase Chain Reaction; Muscle Hypotonia; Muscle Weakness; Muscular Atrophy, Spinal*; Neuromuscular Diseases; Neuronal Apoptosis-Inhibitory Protein; Phenotype; Polymerase Chain Reaction; Retrospective Studies; Ventilators, Mechanical
- From:Journal of Clinical Neurology 2017;13(1):27-31
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND AND PURPOSE: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscle weakness and atrophy. Most SMA patients have a homozygous deletion in survival of motor neuron 1 (SMN1) gene, and neuronal apoptosis inhibitory protein (NAIP) gene is considered a phenotype modifier. We investigated the genotype-phenotype correlation of SMN1 and NAIP deletions in Korean SMA patients. METHODS: Thirty-three patients (12 males and 21 females) treated at the Asan Medical Center between 1999 and 2013 were analyzed retrospectively. The polymerase chain reaction (PCR), restriction-fragment-length polymorphism analysis, and multiplex PCR were used to detect deletions in SMN1 (exons 7 and 8) and NAIP (exons 4 and 5). We reviewed clinical presentations and outcomes and categorized the patients into three clinical types. NAIP deletion-driven differences between the two genotypes were analyzed. RESULTS: Deletion analysis identified homozygous deletions of SMN1 exons 7 and 8 in 30 patients (90.9%). Among these, compared with patients without an NAIP deletion, those with an NAIP deletion showed a significantly lower age at symptom onset (1.9±1.7 months vs. 18.4±20.4 months, mean±SD; p=0.007), more frequent type 1 phenotype (6/6 vs. 8/24, p=0.005), and worse outcomes, with early death or a requirement for ventilator support (4/4 vs. 2/12, p=0.008). CONCLUSIONS: Homozygous deletion in SMN1 and a concurrent NAIP deletion were associated with an early onset, severe hypotonia, and worse outcome in SMA patients. Deletion analysis of NAIP and SMN1 can help to accurately predict prognostic outcomes in SMA.
