KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Joanna KennedyRuth Newbury-Ecob

Abstract

Pathogenic variants in KAT6A have recently been identified as a cause of syndromic developmental delay. Within 2 years, the number of patients identified with pathogenic KAT6A variants has rapidly expanded and the full extent and variability of the clinical phenotype has not been reported. We obtained data for patients with KAT6A pathogenic variants through three sources: treating clinicians, an online family survey distributed through social media, and a literature review. We identified 52 unreported cases, bringing the total number of published cases to 76. Our results expand the genotypic spectrum of pathogenic variants to include missense and splicing mutations. We functionally validated a pathogenic splice-site variant and identified a likely hotspot location for de novo missense variants. The majority of clinical features in KAT6A syndrome have highly variable penetrance. For core features such as intellectual disability, speech delay, microcephaly, cardiac anomalies, and gastrointestinal complications, genotype- phenotype correlations show that late-truncating pathogenic variants (exons 16-17) are significantly more prevalent. We highlight novel associations, including an increased risk of gastrointestinal obstruction. O...Continue Reading

References

Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Dec 7, 2010·Cellular and Molecular Life Sciences : CMLS·Vasileia Sapountzi, Jacques Côté
Jul 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Kim L Good-JacobsonDavid Tarlinton
Oct 19, 2014·JAMA : the Journal of the American Medical Association·Hane LeeStanley F Nelson
Mar 3, 2015·American Journal of Human Genetics·Emma ThamAnn Nordgren
May 3, 2016·American Journal of Medical Genetics. Part a·Francisca MillanSherri Bale
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Sep 13, 2016·American Journal of Medical Genetics. Part a·Alexandra Gauthier-VasserotJulien Thevenon
Sep 23, 2016·Cell Reports·Dane M NewmanRhys S Allan
Nov 20, 2016·Genome Biology·Nicholas Katsanis
Dec 3, 2016·Nucleic Acids Research·UNKNOWN The UniProt Consortium
Dec 14, 2016·The New England Journal of Medicine·Jennifer E PoseyJames R Lupski
Jan 31, 2017·Nature·UNKNOWN Deciphering Developmental Disorders Study
Jun 22, 2017·American Journal of Medical Genetics. Part a·Nitash Zwaveling-SoonawalaRaoul C M Hennekam
Jun 27, 2017·Clinical and Translational Allergy·Varpu EleniusTuomas Jartti
Jan 1, 2017·Human Genome Variation·Chisei SatohKoh-Ichiro Yoshiura

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Citations

Jan 10, 2020·Nature·Melina ClaussnitzerMark I McCarthy
Dec 3, 2020·Cellular and Molecular Life Sciences : CMLS·Britt MossinkNael Nadif Kasri
Jan 3, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Simranpreet KaurJohn Christodoulou
Nov 19, 2020·Diseases·Irene Villalón-GarcíaJosé Antonio Sánchez-Alcázar
Feb 9, 2021·Journal of Pediatric Genetics·Fady P MarjiJoseph E Losee
Mar 27, 2021·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Nisha KorakaviCasey Madura
May 8, 2021·Frontiers in Cell and Developmental Biology·Chiara ParodiValentina Massa
May 28, 2021·Journal of Pediatric Ophthalmology and Strabismus·LeAnne YoungElias I Traboulsi
Jul 21, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Emily G MillerMeghan C Halley
Aug 29, 2021·Pharmaceuticals·Marcin JanowskiAleksandra Pękowska
Aug 28, 2021·Brain Sciences·Clay Smith, Jacqueline Harris
Oct 26, 2021·Pediatric Hematology and Oncology·Chengfang ZhangYong Sun

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Methods Mentioned

BETA
exome sequencing
acetylation

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