Exome Sequencing Identifies a Novel SIN3A Variant in a Patient with Witteveen-Kolk Syndrome

Monica Penon-Portmann; Colleen M Carlston; Pierre-Marie Martin; Anne Slavotinek

doi:10.1159/000520042

Exome Sequencing Identifies a Novel SIN3A Variant in a Patient with Witteveen-Kolk Syndrome

Mol Syndromol. 2022 Jul;13(4):337-342. doi: 10.1159/000520042. Epub 2022 Feb 25.

Authors

Monica Penon-Portmann^{1

2}, Colleen M Carlston¹, Pierre-Marie Martin², Anne Slavotinek^{1

2}

Affiliations

¹ Division of Medical Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.
² Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA.

Abstract

Witteveen-Kolk syndrome (WITKOS; OMIM #613406) is a recently described, rare neurodevelopmental syndrome characterized by mild intellectual disability and a recognizable facial gestalt. WITKOS is caused by heterozygous loss-of-function variants in SIN3A. It shares some features with 15q24 deletion syndrome but to date has only been described in a limited number of patients mostly of Northern European ancestry. Here, we report the first patient with Hispanic ancestry to our knowledge diagnosed with WITKOS, who has a novel, truncating variant in the SIN3A gene. Clinical exome sequencing performed in-house using a custom bioinformatics pipeline identified a de novo heterozygous, nonsense variant in SIN3A, c.1015C>T (p.Gln339Ter) that has not been previously described in the literature. This 3-year-old boy with WITKOS demonstrated classic features including mild developmental delay and triangular facies with hypotelorism and deep-set, hooded eyes. This patient supports the currently described phenotype for WITKOS in more diverse populations.

Keywords: 15q24 deletion; Developmental delay; Diverse populations; SIN3A; Witteveen-Kolk syndrome.

Publication types

Case Reports