Article
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
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Flores-Contreras E, A, García-Ortiz J, E, Robles-Espinoza C, D, Zomosa-Signoret V, Becerra-Solano L, E, Vidaltamayo R, Castaneda-García C, Esparza-García E, Molina-Aguilar C, Hernández-Orozco A, A, Córdova-Fletes C: 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 <b><i>NEU1</i></b>. Mol Syndromol 2021;12:250-257. doi: 10.1159/000515081
1661-8777
Autor
Flores Contreras, Elda Ariadna
García Ortiz, José Elías
Robles Espinoza, Carla Daniela
Zomosa Signoret, Viviana
Becerra Solano, Luis Eduardo
Vidaltamayo, Román
Castaneda García, Carolina
Esparza García, Eduardo
Molina Aguilar, Christian
Hernández Orozco, Angélica Alejandra
Córdova Fletes, Carlos
Institución
Resumen
Artículo Abstract
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.