An uncommon inheritance pattern in Niemann-Pick disease type C: identification of probable paternal germline mosaicism in a Mexican familyReportar como inadecuado




An uncommon inheritance pattern in Niemann-Pick disease type C: identification of probable paternal germline mosaicism in a Mexican family - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Neurology

, 16:147

Neurogenetics

Abstract

BackgroundNiemann-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 presentationWe 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.

ConclusionsWe 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.

KeywordsGermline mosaicism Genetic counseling Lysosomal storage disease Niemann-Pick disease type C NPC1 mutations  Download fulltext PDF



Autor: Marivi Cervera-Gaviria - Miguel Angel Alcántara-Ortigoza - Ariadna González-del Angel - Paola Moyers-Pérez - Blanca Gabri

Fuente: https://link.springer.com/







Documentos relacionados