J Clin Neurol.  2017 Jan;13(1):27-31. 10.3988/jcn.2017.13.1.27.

Genotype-Phenotype Correlation of SMN1 and NAIP Deletions in Korean Patients with Spinal Muscular Atrophy

• Ahn EJ
• Yum MS
• Kim EH
• Yoo HW
• Lee BH
• Kim GH
• Ko TS

• KMID: 2364894
• DOI: http://doi.org/10.3988/jcn.2017.13.1.27

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.

Keyword

spinal muscular atrophy; SMN1; NAIP; genotype; phenotype

MeSH Terms

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
Neuronal Apoptosis-Inhibitory Protein

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