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The First Patient with Tibial Hemimelia-Polysyndactyly-Triphalangeal Thumb Syndrome Caused by De Novo c.423+4916 T>C ZRS Variant: A Case Report.
Zepeda-Olmos, Paola Montserrat; Robles-Espinoza, Kiabeth; Esparza-García, Eduardo; Magaña-Torres, María Teresa.
Afiliación
  • Zepeda-Olmos PM; División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Independencia Oriente, Guadalajara 44340, Jalisco, Mexico.
  • Robles-Espinoza K; Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Independencia Oriente, Guadalajara 44340, Jalisco, Mexico.
  • Esparza-García E; División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Independencia Oriente, Guadalajara 44340, Jalisco, Mexico.
  • Magaña-Torres MT; Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Sierra Mojada 950, Independencia Oriente, Guadalajara 44340, Jalisco, Mexico.
Int J Mol Sci ; 25(17)2024 Aug 29.
Article en En | MEDLINE | ID: mdl-39273297
ABSTRACT
Genetic variants in the zone of polarizing activity regulatory sequence (ZRS) that induce ectopic expression of the SHH gene have been associated with different ZRS-related phenotypes. We report the first patient with a de novo variant, c.423+4916 T>C, in ZRS (previously classified as a variant of uncertain significance) that causes tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome (THPTTS). A two-month-old male patient presented with bilateral preaxial polydactyly, triphalangeal thumb, and tibial agenesis and was heterozygous for the variant c.423+4916T>C (neither of his parents was a carrier). The findings obtained from the family study were sufficient to reclassify the variant from "uncertain significance" to "likely pathogenic" according to three criteria from the American College of Medical Genetics and Genomics guidelines, as follows (1) absence of gnomAD, (2) confirmation of paternity and maternity, and (3) strong phenotype-genotype association. In ZRS-associated syndromes, a wide clinical spectrum has been observed, ranging from polydactyly to THPTTS; our patient has the most severe and rare phenotype. We did not perform functional assays. However, the c.423+4916T>C variant is flanked by three variants, which have been proven not only to cause the phenotype but also to increase the expression of SHH. Through all this data gathering, we consider the c.423+4916T>C variant to be causative of THPTTS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pulgar / Deformidades Congénitas de la Mano / Ectromelia Límite: Humans / Infant / Male Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: México Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pulgar / Deformidades Congénitas de la Mano / Ectromelia Límite: Humans / Infant / Male Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: México Pais de publicación: Suiza