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http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/1348| Título : | An uncommon inheritance pattern in Niemann-Pick disease type C: Identification of probable paternal germline mosaicism in a Mexican family |
| Creador: | Cervera Gaviria M., |
| Nivel de acceso: | Open access |
| Palabras clave : | Exones Humanos Patrón de Herencia Masculino Mosaicismo Mutación Enfermedad de Niemann-Pick Tipo C - genética Probabilidad Adulto Joven Exons Humans Inheritance Patterns Male Mosaicism Mutation Niemann-Pick Disease, Type C - genetics Probability Young Adult Asesoramiento Genético Mosaicismo Enfermedades por Almacenamiento Lisosomal Enfermedad de Niemann-Pick Tipo C NPC1 mutaciones Genetic counseling; Germline mosaicism; Lysosomal storage disease; Niemann-Pick disease type C; NPC1 mutations |
| Descripción : | Background: Niemann-Pick disease type C (NP-C) is a fatal lysosomal neurodegenerative and neurovisceral disease. It is caused by defects in intracellular lipid trafficking, which lead to the accumulation of lipids and glycosphingolipids within the endosomes and lysosomes of affected individuals. Pathogenic variants of the NPC1 or NPC2 genes yield highly variable phenotypes with a time course that ranges from fetal onset (i.e., hydrops fetalis) to progressive dementia in adults. NP-C is typically inherited in an autosomal-recessive manner. To our knowledge, no previous report has identified germline mosaicism as an inheritance mechanism in NP-C. Case presentation: We report the case of a male Mexican patient with "variant" filipin staining and a juvenile form of NP-C attributed to compound heterozygosity for two previously reported pathogenic variants of NPC1: c.[1042C>T];[2780C>T] or p.[Arg348*];[Ala927Val]. The proband's mother and healthy sister were heterozygous carriers of the c.2780C > T (exon 18) and c.1042C > T (exon 8) variants, respectively. However, direct sequencing of exons 8 and 18 of NPC1 revealed no mutation in genomic DNA obtained from the father's peripheral blood. DNA profiling ruled out the possibility of non-paternity. We were unable to obtain a sperm sample to demonstrate paternal gonadal mosaicism. NPC1 haplotype analysis using 20 linked single nucleotide variants failed to yield sufficient information to document a p.(Arg348*) NPC1 pathogenic variant-associated haplotype in the family. Conclusions: We propose that this case of NP-C involves paternal germline mosaicism. To the best of our knowledge, this has not previously been reported in NP-C. © 2016 The Author(s). |
| Colaborador(es) u otros Autores: | Alcántara-Ortigoza M.A. González-del Angel A. Moyers-Pérez P. Legorreta-Ramírez B.G.L. Barrera-Carmona N. Cervera-Gaviria J. |
| Fecha de publicación : | 2016 |
| Tipo de publicación: | Artículo |
| Formato: | |
| Identificador del Recurso : | 10.1186/s12883-016-0649-5 |
| Fuente: | BMC Neurology 16(1):1-6 |
| URI : | http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/1348 |
| Idioma: | eng |
| Aparece en las colecciones: | Artículos |
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