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.
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Acknowledgements
We would like to thank the patients, families and clinicians who have contributed to this report. AEF was supported by the Wales Gene Park. Wales Gene Park is a Health and Care Research Wales funded infrastructure support group. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [grant number HICF-1 009-003]. This study makes use of DECIPHER (http://decipher.sanger.ac.uk), which is funded by Wellcome. See Nature PMID: 25533962 or www.ddduk.org/access.html for full acknowledgement. Clinical testing and analysis were performed by The Department of Medical Genetics, Telemark Hospital Trust, Skien, Norway and the Exeter Genomics Laboratory, Royal Devon & Exeter NHS Foundation Trust, UK.
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Individuals who had evaluation or analysis beyond routine clinical care were part of research studies approved by the Cambridge South Research Ethics Committee (10/H0305/83).
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Murch, O., Jain, V., Benneche, A. et al. Further delineation of the clinical spectrum of White–Sutton syndrome: 12 new individuals and a review of the literature. Eur J Hum Genet 30, 95–100 (2022). https://doi.org/10.1038/s41431-021-00961-3
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DOI: https://doi.org/10.1038/s41431-021-00961-3
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