Further delineation of the clinical spectrum of White–Sutton syndrome: 12 new individuals and a review of the literature
- 14 October 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in European Journal of Human Genetics
- Vol. 30 (1), 95-100
- https://doi.org/10.1038/s41431-021-00961-3
Abstract
White–Sutton syndrome (WHSUS) is a neurodevelopmental disorder caused by heterozygous loss-of-function variants in POGZ. Through the Deciphering Developmental Disorders study and clinical testing, we identified 12 individuals from 10 families with pathogenic or likely pathogenic variants in POGZ (eight de novo and two inherited). Most individuals had delayed development and/or intellectual disability. We analyzed the clinical findings in our series and combined it with data from 89 previously reported individuals. The results demonstrate WHSUS is associated with variable developmental delay or intellectual disability, increased risk of obesity, visual defects, craniofacial dysmorphism, sensorineural hearing loss, feeding problems, seizures, and structural brain malformations. Our series includes further individuals with rod-cone dystrophy, cleft lip and palate, congenital diaphragmatic hernia, and duplicated renal drainage system, suggesting these are rare complications of WHSUS. In addition, we describe an individual with a novel, de novo missense variant in POGZ and features of WHSUS. Our work further delineates the phenotypic spectrum of WHSUS highlighting the variable severity of this disorder and the observation of familial pathogenic POGZ variants.This publication has 29 references indexed in Scilit:
- Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research dataThe Lancet, 2014
- The contribution of de novo coding mutations to autism spectrum disorderNature, 2014
- Synaptic, transcriptional and chromatin genes disrupted in autismNature, 2014
- Genome sequencing identifies major causes of severe intellectual disabilityNature, 2014
- De novo mutations in schizophrenia implicate synaptic networksNature, 2014
- De Novo Gene Disruptions in Children on the Autistic SpectrumNeuron, 2012
- Human POGZ modulates dissociation of HP1α from mitotic chromosome arms through Aurora B activationNature, 2010
- DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl ResourcesAmerican Journal of Human Genetics, 2009
- HP1 Proteins Form Distinct Complexes and Mediate Heterochromatic Gene Silencing by Nonoverlapping MechanismsMolecular Cell, 2008
- Maintenance of Stable Heterochromatin Domains by Dynamic HP1 BindingScience, 2003