Dataset Information

Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2.

ABSTRACT:

Purpose

The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood.

Methods

Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed.

Results

Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified. Missense variants clustered in the TRP 2, 3, 7 and Jmj-C domains. Truncating variants were significantly more likely to be de novo. Thirteen individuals had maternally inherited variants and one had a paternally inherited variant. Neonatal feeding difficulties, hypoglycemia, postnatal growth retardation, poor weight gain, motor delay, intellectual disability (ID), microcephaly, congenital heart anomalies, palate defects, renal malformations, strabismus, hearing loss, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and gastroesophageal reflux were frequent clinical findings. Facial features of over a third of patients were not typical for KS. Males were significantly more likely to be born prematurely, have shorter stature, and severe developmental delay/ID.

Conclusion

We expand the KDM6A variant spectrum and delineate the KS2 phenotype. We demonstrate that the variability of the KS2 phenotypic depends on sex and the variant type. We also highlight the overlaps and differences between the phenotypes of KS2 and KS1.

SUBMITTER: Faundes V

PROVIDER: S-EPMC8257478 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2.

Faundes Víctor V Goh Stephanie S Akilapa Rhoda R Bezuidenhout Heidre H Bjornsson Hans T HT Bradley Lisa L Brady Angela F AF Brischoux-Boucher Elise E Brunner Han H Bulk Saskia S Canham Natalie N Cody Declan D Dentici Maria Lisa ML Digilio Maria Cristina MC Elmslie Frances F Fry Andrew E AE Gill Harinder H Hurst Jane J Johnson Diana D Julia Sophie S Lachlan Katherine K Lebel Robert Roger RR Byler Melissa M Gershon Eric E Lemire Edmond E Gnazzo Maria M Lepri Francesca Romana FR Marchese Antonia A McEntagart Meriel M McGaughran Julie J Mizuno Seiji S Okamoto Nobuhiko N Rieubland Claudine C Rodgers Jonathan J Sasaki Erina E Scalais Emmanuel E Scurr Ingrid I Suri Mohnish M van der Burgt Ineke I Matsumoto Naomichi N Miyake Noriko N Benoit Valérie V Lederer Damien D Banka Siddharth S

Genetics in medicine : official journal of the American College of Medical Genetics 20210305 7

<h4>Purpose</h4>The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood.<h4>Methods</h4>Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed.<h4>Results</h4>Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified. Missense variants clustered in the TRP 2, 3, 7 and Jmj-C domains. Truncating variants were signific ...[more]

PMID: 33674768

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Dataset Information

Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2.

Purpose

Methods

Results

Conclusion

Publications

Clinical delineation, sex differences, and genotype-phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2.

Similar Datasets

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