Clinical Exome Sequencing Enables Congenital Sialidosis Type II Diagnosis in Two Siblings Presenting with Unreported Clinical Features from a Rare Homozygous Sequence Variant p.(Tyr370Cys) in NEU1 .

Autor:	Flores-Contreras EA; Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico., García-Ortiz JE; División de Genética, Centro de Investigación Biomédica de Occidente, CMNO-IMSS, Guadalajara, Mexico., Robles-Espinoza CD; Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Campus Juriquilla, Santiago de Querétaro, Mexico.; Wellcome Sanger Institute, Hinxton, United Kingdom., Zomosa-Signoret V; Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico., Becerra-Solano LE; División de Ciencias Biomédicas, Departamento de Clínicas, CUALTOS Universidad de Guadalajara, Tepatitlán, Mexico., Vidaltamayo R; Department of Basic Science, School of Medicine, Universidad de Monterrey, San Pedro GG, Mexico., Castaneda-García C; Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Campus Juriquilla, Santiago de Querétaro, Mexico., Esparza-García E; UMAE Hospital de Pediatría, CMNO-IMSS, Guadalajara, Mexico., Molina-Aguilar C; Laboratorio Internacional de Investigación sobre el Genoma Humano, Universidad Nacional Autónoma de México, Campus Juriquilla, Santiago de Querétaro, Mexico.; Centre of Bioengineering, School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey, Mexico., Hernández-Orozco AA; División de Genética, Centro de Investigación Biomédica de Occidente, CMNO-IMSS, Guadalajara, Mexico., Córdova-Fletes C; Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
Jazyk:	angličtina
Zdroj:	Molecular syndromology [Mol Syndromol] 2021 Jul; Vol. 12 (4), pp. 250-257. Date of Electronic Publication: 2021 Jun 17.
DOI:	10.1159/000515081
Abstrakt:	Sialidosis is a rare autosomal recessive disease that presents with progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by homozygous or compound heterozygous sequence variants in the neuraminidase 1 ( NEU1 ) gene. These sequence variants can lead to sialidosis type I and II; the latter is the most severe and presents prenatally or at early age. However, sialidosis diagnosis is challenging, especially in those health systems with limited resources of developing countries. Consequently, it is necessary to dip into high-throughput molecular diagnostic tools to allow for an accurate diagnosis with better cost-effectiveness and turnaround time. We report a 4-member pedigree segregating an ultrarare missense variant, c.1109A>G; p.Tyr370Cys, in NEU1 as detected by whole-exome sequencing. Two short-lived siblings, who presented with previously unreported clinical features from such a homozygous sequence variant, were diagnosed with sialidosis type II. Additionally, we present a novel molecular model exhibiting the consequences of the variant in the sialidase-1 tridimensional structure. This study allowed us to provide a definitive diagnosis for our patients, increase our understanding of this pathogenic variant, and improve genetic counseling. Competing Interests: The authors have no conflicts of interest to declare. (Copyright © 2021 by S. Karger AG, Basel.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu