Niemann-Pick disease A or B in four pediatric patients and SMPD1 mutation carrier frequency in the Mexican population
Por:
Ceron-Rodriguez, Magdalena, Vázquez-Martínez E.R., Garcia-Delgado, Constanza, Ortega-Vazquez, Alberto, Valencia-Mayoral, Pedro, Ramirez-Devars, Lyuva, Arias-Villegas, Christian, Monroy-Muñoz I.E., Lopez, Marisol, Cervantes, Alicia, Cerbon, Marco, Morán-Barroso V.F.
Publicada:
1 ene 2019
Resumen:
INTRODUCTION AND OBJECTIVES: Niemann-Pick disease type A (NPD-A) and B (NPD-B) are lysosomal storage diseases with a birth prevalence of 0.4-0.6/100,000. They are caused by a deficiency in acid sphingomyelinase, an enzyme encoded by SMPD1. We analyzed the phenotype and genotype of four unrelated Mexican patients, one with NPD-A and three with NPD-B. PATIENTS AND METHODS: Four female patients between 1 and 7 years of age were diagnosed with NPD-A or NPD-B by hepatosplenomegaly, among other clinical characteristics, and by determining the level of acid sphingomyelinase enzymatic activity and sequencing of the SMPD1 gene. Additionally, a 775bp amplicon of SMPD1 (from 11:6393835_6394609, including exons 5 and 6) was analyzed by capillary sequencing in a control group of 50 unrelated healthy Mexican Mestizos. RESULTS: An infrequent variant (c.1343A>G p.Tyr448Cys) was observed in two patients. One is the first NPD-A homozygous patient reported with this variant and the other a compound heterozygous NPD-B patient with the c.1829_1831delGCC p.Arg610del variant. Another compound heterozygous patient had the c.1547A>G p.His516Arg variant (not previously described in affected individuals) along with the c.1805G>A p.Arg602His variant. A new c.1263+8C>T pathogenic variant was encountered in a homozygous state in a NPD-B patient. Among the healthy control individuals there was a heterozygous carrier for the c.1550A>T (rs142787001) pathogenic variant, but none with the known pathogenic variants in the 11:6393835_6394609 region of SMPD1. CONCLUSIONS: The present study provides further NPD-A or B phenotype-genotype correlations. We detected a heterozygous carrier with a pathogenic variant in 1/50 healthy Mexican mestizos. Copyright © 2019 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.
Filiaciones:
Ceron-Rodriguez, Magdalena:
Lysosomal Disorders Clinic, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
Hosp Infantil Mexico Dr Federico Gomez, Lysosomal Disorders Clin, Mexico City, DF, Mexico
Vázquez-Martínez E.R.:
Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico
Garcia-Delgado, Constanza:
Department of Genetics, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico
Hosp Infantil Mexico Dr Federico Gomez, Dept Genet, Mexico City, DF, Mexico
Ortega-Vazquez, Alberto:
Department of Biological Systems, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
Univ Autonoma Metropolitana Xochimilco, Dept Biol Syst, Mexico City, DF, Mexico
Valencia-Mayoral, Pedro:
Department of Pathology, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
Hosp Infantil Mexico Dr Federico Gomez, Dept Pathol, Mexico City, DF, Mexico
Ramirez-Devars, Lyuva:
Lysosomal Disorders Clinic, Hospital Infantil de México Federico Gómez, Mexico City, Mexico
Hosp Infantil Mexico Dr Federico Gomez, Lysosomal Disorders Clin, Mexico City, DF, Mexico
Arias-Villegas, Christian:
Department of Genetics, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico
Hosp Infantil Mexico Dr Federico Gomez, Dept Genet, Mexico City, DF, Mexico
Monroy-Muñoz I.E.:
Departamento de Genética y Genómica Humana, Instituto Nacional de Perinatología, Mexico City, Mexico
Lopez, Marisol:
Department of Biological Systems, Universidad Autónoma Metropolitana-Xochimilco, Mexico City, Mexico
Univ Autonoma Metropolitana Xochimilco, Dept Biol Syst, Mexico City, DF, Mexico
Cervantes, Alicia:
Servicio de Genética, Hospital General de México Dr. Eduardo Liceaga-Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Fac Med, Hosp Gen Mexico Dr Eduardo Liceaga, Serv Genet, Mexico City, DF, Mexico
Cerbon, Marco:
Unidad de Investigación en Reproducción Humana, Instituto Nacional de Perinatología-Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Unidad Invest Reprod Humana, Inst Nacl Perinatol, Fac Quim, Mexico City, DF, Mexico
Morán-Barroso V.F.:
Department of Genetics, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico
Inst Nacl Perinatol, Dept Genet & Genom Humana, Mexico City, DF, Mexico
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