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Clinical, biochemical, and genotype-phenotype correlations of 118 patients with Niemann-Pick disease Types A/B.
Hu, Jiayue; Maegawa, Gustavo H B; Zhan, Xia; Gao, Xiaolan; Wang, Yu; Xu, Feng; Qiu, Wenjuan; Han, Lianshu; Gu, Xuefan; Zhang, Huiwen.
Afiliação
  • Hu J; Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Maegawa GHB; Departments of Pediatrics Genetics and Metabolism, Neuroscience, Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, USA.
  • Zhan X; Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Gao X; Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang Y; Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Xu F; Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Qiu W; Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Han L; Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Gu X; Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhang H; Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hum Mutat ; 42(5): 614-625, 2021 05.
Article em En | MEDLINE | ID: mdl-33675270
Niemann-Pick disease Types A and B (NPA/B) are autosomal recessive disorders caused by variants in the sphingomyelin phosphodiesterase-1 (SMPD1) gene. This study aimed to describe and characterize a cohort of 118 patients diagnosed with NPA/B based on clinical, biochemical, and molecular findings, and to identify sound correlations between laboratory findings and clinical presentations. Decreased peripheral leukocyte acid sphingomyelinase activity levels and increased plasma 7-ketocholesterol levels were significantly correlated with disease onset and severity of the clinical course. We identified 92 different sequence SMPD1 variants, including 41 novel variants, in 118 NPA/B patients (19 NPA, 24 intermediate type, 75 NPB). The most prevalent mutation was p.Arg602His, which accounted for 9.3% of the alleles. Patients homozygous for p.Arg602His or p.Asn522Ser showed a late-onset form of the NPB phenotype. The homozygous SMPD1 variant p.Tyr500His correlated with the early-onset NPB clinical form. Additionally, homozygous variants p.His284SerfsX18, p.Phe465Ser, and p.Ser486Arg were associated with the neuronopathic NPA clinical form. The homozygous variant p.Arg3AlafsX74 was associated with the intermediate clinical form. Our study contributes to the understanding of the natural history of NPA/B and assists in the development of efficacious treatments for patients afflicted with this devastating lysosomal storage disorder.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esfingomielina Fosfodiesterase / Doença de Niemann-Pick Tipo A Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esfingomielina Fosfodiesterase / Doença de Niemann-Pick Tipo A Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article