Niemann-Pick Disease Type C: Mutation Spectrum and Novel Sequence Variations in the Human NPC1 Gene.
Mol Neurobiol
; 56(9): 6426-6435, 2019 Sep.
Article
en En
| MEDLINE
| ID: mdl-30820861
ABSTRACT
Niemann-Pick type C (NP-C) is a rare autosomal recessive disorder characterized by storage of unesterified glycolipids and cholesterol in lysosome and/or late endosome due to mutations in either NPC1 or NPC2 gene. This study aims to identify the spectrum of sequence alterations associated to NP-C in individuals with clinical suspicion of this disease. The entire coding region and flanking sequences of both genes associated to NP-C were evaluated in a total of 265 individuals that were referred to our laboratory. Clinical and/or biochemical suspicion of NP-C was confirmed by molecular analysis in 54 subjects. In this cohort, 33 different sequence alterations were identified in NPC1 and one in NPC2. Among those, 5 novel alterations in NPC1 gene were identified as follows one deletion (p.Lys38_Tyr40del), one frameshift (p.Asn195Lysfs*2), and three missense mutations (p.Cys238Arg, p.Ser365Pro and, p.Val694Met) that are likely to be pathogenic through different approaches, including in silico tools as well as multiple sequence alignment throughout different species. We have also reported main clinical symptoms of patients with novel alterations and distribution of frequent symptoms in the cohort. Findings reported here contribute to the knowledge of mutation spectrum of NP-C, defining frequent mutations as well as novel sequence alterations associated to the disease.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos y Proteínas de Señalización Intracelular
/
Enfermedad de Niemann-Pick Tipo C
/
Mutación
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
/
Adult
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Mol Neurobiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Brasil