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. 2018 Oct 11;13(1):178.
doi: 10.1186/s13023-018-0909-0.

Description of the molecular and phenotypic spectrum of Wiedemann-Steiner syndrome in Chinese patients

Niu Li  1   2 , Yirou Wang  3 , Yu Yang  4 , Pengpeng Wang  5 , Hui Huang  6 , Shiyi Xiong  7 , Luming Sun  7 , Min Cheng  8 , Cui Song  9 , Xinran Cheng  10 , Yu Ding  3 , Guoying Chang  3 , Yao Chen  3 , Yufei Xu  1 , Tingting Yu  1   2 , Ru-En Yao  1   2 , Yiping Shen  1   11 , Xiumin Wang  12   13 , Jian Wang  14   15   16
Affiliations

Description of the molecular and phenotypic spectrum of Wiedemann-Steiner syndrome in Chinese patients

Niu Li et al. Orphanet J Rare Dis. .

Abstract

Background: Wiedemann-Steiner syndrome (WDSTS) is a rare genetic disorder characterized by facial gestalt, neurodevelopmental delay, skeletal anomalies and growth retardation, which is caused by variation of KMT2A gene. To date, only 2 Chinese WDSTS patients have been reported. Here, we report the phenotypes and KMT2A gene variations in 14 unrelated Chinese WDSTS patients and investigate the phenotypic differences between the Chinese and French cohorts.

Methods: Next generation sequencing was performed for each patient, and the variants in the KMT2A gene were validated by Sanger sequencing. The phenotypes of 16 Chinese WDSTS patients were summarized and compared to 33 French patients.

Results: Genetic sequencing identified 13 deleterious de novo KMT2A variants in 14 patients, including 10 truncating, 2 missenses and 1 splicing variants. Of the 13 variants, 11 are novel and two have been reported previously. One of the patients is mosaic in the KMT2A gene. The variation spectra and phenotypic profiles of the Chinese WDSTS patients showed no difference with patients of other ethnicities; however, differ in the frequencies of several clinical features. We demonstrated that variations in the KMT2A gene can lead to both advanced and delayed bone age. We identified 6 novel phenotypes, which include microcephaly, deep palmar crease, external ear deformity, carpal epiphyseal growth retardation, dyslipidemia, and glossoptosis. In addition, patients harbored missense variants in the CXXC zinc finger domain of KMT2A showed more severe neurophenotypes.

Conclusion: Our study consists of the largest cohort of Chinese WDSTS patients that continues to expand the WDSTS phenotypic and variation spectrum. Our results support the notion that the CXXC zinc finger domain of KMT2A gene is a hotspot for missense variants associated with more severe neurophenotypes.

Keywords: Chinese patients; KMT2A variation; Phenotypic differences; Wiedemann–Steiner syndrome.

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Conflict of interest statement

Ethics approval and consent to participate

All procedures followed were in accordance with the ethical standards of the responsible institutional committee on human experimentation and with the Helsinki Declaration of 1975 (revised in 2000). The protocols were approved by the Institutional Medical Ethics Committee.

Consent for publication

Informed consent was obtained from each patient’s family.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Phenotypes of the patients. a Facial appearances of patients 1–14. Patients 10 and 12 showed external ear deformity. b Malformations of hands and feet in seven patients. c Hypertrichosis of seven patients
Fig. 2
Fig. 2
X-ray results of Patients 6 and 10. a The bone age of Patient 6 was advanced for 2.5 years. Patient 10 had a bone age of 4.5–5 years old and severe carpal epiphyseal growth retardation (b) and scoliosis (c)
See this image and copyright information in PMC

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