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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2019

Open Access 01-12-2019 | Intellectual Disability | Research

Kabuki syndrome: novel pathogenic variants, new phenotypes and review of literature

Authors: Huakun Shangguan, Chang Su, Qian Ouyang, Bingyan Cao, Jian Wang, Chunxiu Gong, Ruimin Chen

Published in: Orphanet Journal of Rare Diseases | Issue 1/2019

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Abstract

Objective

This study describes 5 novel variants of 7 KMT2D/KDM6A gene and summarizes the clinical manifestations and the mutational spectrum of 47 Chinese Kabuki syndrome (KS) patients.

Methods

Blood samples were collected for whole-exome sequencing (WES) for 7 patients and their parents if available. Phenotypic and genotypic spectra of 40 previously published unrelated Chinese KS patients were summarized.

Result

Genetic sequencing identified six KMT2D variants (c.3926delC, c.5845delC, c.6595delT, c.12630delG, c.16294C > T, and c.16442delG) and one KDM6A variant (c.2668-2671del). Of them, 4 variants (c.3926delC, c.5845delC, c.12630delG, and c.16442delG) in KMT2D gene and the variant (c.2668-2671del) in KDM6A gene were novel. Combining with previously published Chinese KS cases, the patients presented with five cardinal manifestations including facial dysmorphism, intellectual disability, growth retardation, fingertip pads and skeletal abnormalities. In addition, 29.5% (5/17) patients had brain abnormalities, such as hydrocephalus, cerebellar vermis dysplasia, thin pituitary and white matter myelination delay, corpus callosum hypoplasia and Dandy-Walker malformation.

Conclusion

In this report, five novel variants in KMT2D/KDM6A genes are described. A subset of Chinese KS patients presented with brain abnormalities that were not previously reported. Our study expands the mutational and phenotypic spectra of KS.
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Metadata
Title
Kabuki syndrome: novel pathogenic variants, new phenotypes and review of literature
Authors
Huakun Shangguan
Chang Su
Qian Ouyang
Bingyan Cao
Jian Wang
Chunxiu Gong
Ruimin Chen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2019
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-019-1219-x

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