Genotype-Phenotype Correlation ofSMN1andNAIPDeletions in Korean Patients with Spinal Muscular Atrophy
| Autor: | Tae-Sung Ko, Gu-Hwan Kim, Eun Ji Ahn, Eunhee Kim, Mi-Sun Yum, Beom Hee Lee, Han Wook Yoo |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Neuromuscular disease phenotype genotype SMN1 Gastroenterology 03 medical and health sciences 0302 clinical medicine Atrophy NAIP Internal medicine Genotype medicine spinal muscular atrophy business.industry Spinal muscular atrophy medicine.disease SMA Hypotonia 030104 developmental biology Neurology Original Article Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Clinical Neurology (Seoul, Korea) |
| ISSN: | 2005-5013 1738-6586 |
| DOI: | 10.3988/jcn.2017.13.1.27 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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