Genetic and clinical heterogeneity in Korean patients with Rubinstein–Taybi syndrome

Abstract Background Rubinstein–Taybi syndrome (RSTS) is a rare congenital malformation syndrome with clinical characteristics such as hypertrichosis, high arched eyebrows, large beaked nose, and broad thumbs and halluces. RSTS patients showed intellectual disability and health problems such as short...

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Autores principales:	Naye Choi, Hwa Young Kim, Byung Chan Lim, Jong‐Hee Chae, Soo Yeon Kim, Jung Min Ko
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	CREBBP EP300 intellectual disability Rubinstein–Taybi syndrome Genetics QH426-470
Acceso en línea:	https://doaj.org/article/3c3aa8b1be5444b48fb1e853d41902ed
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spelling	oai:doaj.org-article:3c3aa8b1be5444b48fb1e853d41902ed2021-11-10T16:39:23ZGenetic and clinical heterogeneity in Korean patients with Rubinstein–Taybi syndrome2324-926910.1002/mgg3.1791https://doaj.org/article/3c3aa8b1be5444b48fb1e853d41902ed2021-10-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1791https://doaj.org/toc/2324-9269Abstract Background Rubinstein–Taybi syndrome (RSTS) is a rare congenital malformation syndrome with clinical characteristics such as hypertrichosis, high arched eyebrows, large beaked nose, and broad thumbs and halluces. RSTS patients showed intellectual disability and health problems such as short stature, ophthalmologic abnormalities, congenital heart defects, genitourinary defects, and variable types of tumors. Although mutations in CREBBP and EP300 genes are associated with RSTS features, genetic causation is still unknown in 30% of patients. Methods We present clinical and molecular genetic characteristics of 25 unrelated Korean patients clinically diagnosed with RSTS. Sanger sequencing analysis and multiplex ligation‐dependent probe amplification for CREBBP in 25 patients and exome sequencing of CREBBP‐negative cases were performed in nine patients successively. Results Causative variants were identified in 20 (80%) patients: 16 (64%) in CREBBP and 4 (16%) in EP300. All the identified variants predict protein truncation (11 frameshift, 2 nonsense, 1 splicing‐site, and 6 large intragenic deletions); there are no repeatedly identified sequence variants. Four of the CREBBP and all four EP300 variants are novel. Intellectual disability was noted in 24/25 patients (96%); no difference was found between CREBBP and EP300 groups. One patient with a CREBBP variant (4%) had malignant tumor. Conclusions To date, this is the largest cohort of patients with RSTS including EP300‐related patients in Korea. Future large‐scale studies to find genetic mutation of molecularly unsolved patients and long‐term prospective studies are required to validate our results.Naye ChoiHwa Young KimByung Chan LimJong‐Hee ChaeSoo Yeon KimJung Min KoWileyarticleCREBBPEP300intellectual disabilityRubinstein–Taybi syndromeGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CREBBP EP300 intellectual disability Rubinstein–Taybi syndrome Genetics QH426-470
spellingShingle	CREBBP EP300 intellectual disability Rubinstein–Taybi syndrome Genetics QH426-470 Naye Choi Hwa Young Kim Byung Chan Lim Jong‐Hee Chae Soo Yeon Kim Jung Min Ko Genetic and clinical heterogeneity in Korean patients with Rubinstein–Taybi syndrome
description	Abstract Background Rubinstein–Taybi syndrome (RSTS) is a rare congenital malformation syndrome with clinical characteristics such as hypertrichosis, high arched eyebrows, large beaked nose, and broad thumbs and halluces. RSTS patients showed intellectual disability and health problems such as short stature, ophthalmologic abnormalities, congenital heart defects, genitourinary defects, and variable types of tumors. Although mutations in CREBBP and EP300 genes are associated with RSTS features, genetic causation is still unknown in 30% of patients. Methods We present clinical and molecular genetic characteristics of 25 unrelated Korean patients clinically diagnosed with RSTS. Sanger sequencing analysis and multiplex ligation‐dependent probe amplification for CREBBP in 25 patients and exome sequencing of CREBBP‐negative cases were performed in nine patients successively. Results Causative variants were identified in 20 (80%) patients: 16 (64%) in CREBBP and 4 (16%) in EP300. All the identified variants predict protein truncation (11 frameshift, 2 nonsense, 1 splicing‐site, and 6 large intragenic deletions); there are no repeatedly identified sequence variants. Four of the CREBBP and all four EP300 variants are novel. Intellectual disability was noted in 24/25 patients (96%); no difference was found between CREBBP and EP300 groups. One patient with a CREBBP variant (4%) had malignant tumor. Conclusions To date, this is the largest cohort of patients with RSTS including EP300‐related patients in Korea. Future large‐scale studies to find genetic mutation of molecularly unsolved patients and long‐term prospective studies are required to validate our results.
format	article
author	Naye Choi Hwa Young Kim Byung Chan Lim Jong‐Hee Chae Soo Yeon Kim Jung Min Ko
author_facet	Naye Choi Hwa Young Kim Byung Chan Lim Jong‐Hee Chae Soo Yeon Kim Jung Min Ko
author_sort	Naye Choi
title	Genetic and clinical heterogeneity in Korean patients with Rubinstein–Taybi syndrome
title_short	Genetic and clinical heterogeneity in Korean patients with Rubinstein–Taybi syndrome
title_full	Genetic and clinical heterogeneity in Korean patients with Rubinstein–Taybi syndrome
title_fullStr	Genetic and clinical heterogeneity in Korean patients with Rubinstein–Taybi syndrome
title_full_unstemmed	Genetic and clinical heterogeneity in Korean patients with Rubinstein–Taybi syndrome
title_sort	genetic and clinical heterogeneity in korean patients with rubinstein–taybi syndrome
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/3c3aa8b1be5444b48fb1e853d41902ed
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_version_	1718439858427396096

Genetic and clinical heterogeneity in Korean patients with Rubinstein–Taybi syndrome

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