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

Elda Ariadna Flores-Contreras, José Elías García-Ortiz, Carla Daniela Robles-Espinoza, Viviana Zomosa-Signoret, Luis Eduardo Becerra-Solano, Román Vidaltamayo, Carolina Castaneda-García, Eduardo Esparza-García, Christian Molina-Aguilar, Angélica Alejandra Hernández-Orozco, Carlos Córdova-Fletes

Resultado de la investigaciónrevisión exhaustiva

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)250-257
Número de páginas8
PublicaciónMolecular Syndromology
Volumen12
N.º4
DOI
EstadoPublished - 1 jul. 2021

Nota bibliográfica

Publisher Copyright:
© 2021

All Science Journal Classification (ASJC) codes

  • Genética
  • Genética (clínica)

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Profundice en los temas de investigación de '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'. En conjunto forman una huella única.

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