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

Siddharth Srivastava (1) , Erica Macke (2) , Lindsay Swanson (1) , David Coulter (1) , Eric Klee (2) , Sureni Mullegama (3) , Yili Xie (3) , Brendan Lanpher (2) , Emma Bedoukian (4) , Cara Skraban (4) , Laurent Villard (5, 6) , Mathieu Milh (5, 7) , Mary Leppert (8, 9) , Julie Cohen (8, 9)

1 HMS - Harvard Medical School [Boston]
2 Mayo Clinic [Rochester]
3 GeneDx [Gaithersburg, MD, USA]
4 CHOP - Children’s Hospital of Philadelphia
5 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
6 Département de génétique médicale [Hôpital de la Timone - APHM]
7 TIMONE - Hôpital de la Timone [CHU - APHM]
8 Kennedy Krieger Institute [Baltimore]
9 Johns Hopkins University School of Medicine [Baltimore]

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.

Mots clés: WASF1; autism; intellectual disability; neurodevelopmental disorder

Domaines: Sciences du Vivant [q-bio]; Génétique; Médecine humaine et pathologie

Siddharth Srivastava, Erica Macke, Lindsay Swanson, David Coulter, Eric Klee, et al.. Expansion of the Genotypic and Phenotypic Spectrum of WASF1-Related Neurodevelopmental Disorder. Brain Sciences, 2021, 11 (7), pp.931. ⟨10.3390/brainsci11070931⟩. ⟨hal-03664847⟩