Expansion of the Genotypic and Phenotypic Spectrum of WASF1-Related Neurodevelopmental Disorder

Brain Sciences

Brendan C. Lanpher¹  Eric W. Klee¹  Erica L. Macke¹  Laurent Villard²  Julie S. Cohen³  Mary L. O. Leppert³  David Coulter⁴  Lindsay C. Swanson⁴  Siddharth Srivastava⁴  Sureni V. Mullegama⁵  Yili Xie⁵  Mathieu Milh⁶  Emma C. Bedoukian⁷  Cara M. Skraban⁷ 

[1] Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55902, USA;Department of Medical Genetics, AP-HM, La Timone Children’s Hospital, 13385 Marseille, France;Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, MD 21205, USA;Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;GeneDx Inc., Gaithersburg, MD 20877, USA;Inserm, Marseille Medical Genetics Center, Faculté de Médecine de Marseille, Aix Marseille University, 13385 Marseille, France;Roberts Individualized Medical Genetics Center, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA;

关键词: WASF1;    autism;    intellectual disability;    neurodevelopmental disorder;   

DOI  :  10.3390/brainsci11070931

来源: DOAJ

【 摘 要 】

In humans, de novo truncating variants in WASF1 (Wiskott–Aldrich syndrome protein family member 1) have been linked to presentations of moderate-to-profound intellectual disability (ID), autistic features, and epilepsy. Apart from one case series, there is limited information on the phenotypic spectrum and genetic landscape of WASF1-related neurodevelopmental disorder (NDD). In this report, we describe detailed clinical characteristics of six individuals with WASF1-related NDD. We demonstrate a broader spectrum of neurodevelopmental impairment including more mildly affected individuals. Further, we report new variant types, including a copy number variant (CNV), resulting in the partial deletion of WASF1 in monozygotic twins, and three missense variants, two of which alter the same residue, p.W161. This report adds further evidence that de novo variants in WASF1 cause an autosomal dominant NDD.

【 授权许可】

Unknown