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.
Bibliographical noteFunding Information:
This work was supported by CONACYT (INFRA-2013-204423 and S0008-2014-1-233212) for C.C.-F.
We thank the parents who continuously supported this research. E.A.F.-C. was supported by a CONACyT [scholarship No. 334775]. The authors also wish to thank Jair S. García-Sotelo, Alejandro de León, Carlos S. Flores, and Luis A. Aguilar of the Laboratorio Nacional de Visualización Científica Avanzada from the National Autonomous University of Mexico, and Alejandra Castillo, Carina Díaz, Abigayl Hernández and Eglee Lomelin of the International Laboratory for Human Genome Research, UNAM. C.C.-G. is a PhD student from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM) and is supported by CONACyT [scholarship No. 385365].
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