Mosaicism of a Truncating Variant of CASK Causes Congenital Heart Disease and Neurodevelopmental Disorder

Molecular syndromology

article

Ida, Kazumi¹  Kurosawa, Kenji¹  Abe-Hatano, Chihiro¹  Yokoi, Takayuki¹ 

[1] Division of Medical Genetics, Kanagawa Children’s Medical Center

关键词: CASK;    Mosaicism;    Truncating variant;    Congenital heart disease;    Neurodevelopmental disorders;   

DOI  :  10.1159/000524375

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

Introduction: Calcium/calmodulin-dependent serine protein kinase (CASK) gene mutations cause microcephaly with pontine and cerebellar hypoplasia (MICPCH) and X-linked intellectual disability. Congenital heart disease (CHD) is a rare complication reported in only 4 male patients with full loss-of-function mutations. Here, we report the first male patient with mosaicism of a truncating variant of CASK complicated by CHD. Case Presentation: The patient is a 6-year-old male with MICPCH, ventricular septal defect, and developmental delay. He achieved rolling over but can not speak meaningful words. We identified a somatic mosaic variant of CASKA], p.(W242*) and high mosaic ratios of 90% and 84% for mutant alleles in peripheral blood lymphocytes and skin fibroblasts, respectively. His developmental delay was severe but milder than that of previously reported CHD patients. Discussion: Truncating CASK variants may be associated with CHD, even in a mosaic state, and even a low normal allele ratio could lengthen survivorship.

【 授权许可】

CC BY