title: Genotype-Phenotype Correlation of SMN1 and NAIP Deletions in Korean Patients with Spinal Muscular Atrophy.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Ahn
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Yum
authors.affiliation: Department of Pediatrics, CHA Gangnam Medical Center, CHA University, Seoul, Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.|Department of Medical Genetics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Han Wook
authors.initials: HW
authors.lastname: Yoo
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.|Department of Medical Genetics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Beom Hee
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Medical Genetics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Gu Hwan
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea. tsko@amc.seoul.kr.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Ko
keywords: NAIP; SMN1; genotype; phenotype; spinal muscular atrophy