A Chinese Boy with Mowat–Wilson Syndrome Caused by a 10 bp Deletion in the ZEB2 Gene

Abstract

Purpose Mowat–Wilson syndrome (MWS) is a rare complex malformation syndrome which is characterized by typical facial dysmorphism, moderate to severe intellectual disability, global developmental delay, and multiple congenital anomalies. Here, we summarize the clinical characteristics and gene mutation analysis of a Chinese boy with MWS. Patients and Methods The clinical features of the patient were monitored. DNA extracted from peripheral blood was subjected to sequencing analysis. Then, the whole-exome sequencing was performed. Results A novel deletion mutation (c.1137_1146del TAGTATGTCT) was identified in exon 8 of the ZEB2 gene. The deletion mutation was predicted to produce a truncated protein (p.S380Nfs*13), resulting in haploinsufficiency. The patient presented with short stature, microcephaly, congenital heart defects, cryptorchidism, corpus callosum agenesis, global developmental delay, and intellectual disability. Furthermore, he demonstrated bilateral sensorineural hearing loss. This manifestation is less common in MWS. It is first reported in Chinese patients with MWS. Clinical follow-up showed that the facial features of MWS developed with time. The facial features of the patient were not obvious except for the uplifted ear lobes at the age of 3 months. At the age of 22 months, the facial characteristics of the patient included ocular hypertelorism, frontal bossing, rounded nasal tip, sparse eyebrows, prominent chin, widely spaced teeth, and uplifted ear lobes with a central depression. Conclusion A novel deletion mutation of the ZEB2 gene was identified. This work contributes to expanding the mutation spectra of MWS. Our results may reflect the variability of the phenotype in MWS.

Three Novel De Novo ZEB2 Variants Identified in Three Unrelated Chinese Patients With Mowat-Wilson Syndrome and A Systematic Review

“…To date, more than 300 individuals with MWS have been reported in different regions of the world. And nearly 280 variants in ZEB2 have been identified (HGMD database; Wei et al, 2021 ; Zhang et al, 2021 ; Hu et al, 2020 ; Ma et al, 2020 ; Zou et al, 2020 ) ( Supplementary Table S1 ). However, Chinese MWS individuals have been infrequently reported ( Supplementary Table S2 ).…”

“…To date, more than 300 individuals with MWS have been reported in the literature, and approximately 280 variants in ZEB2 have been identified (HGMD database; Wei et al, 2021 ; Zhang et al, 2021 ; Hu et al, 2020 ; Ma et al, 2020 ; Zou et al, 2020 ). However, Chinese MWS individuals are relatively less described, and only 27 MWS cases and 23 pathogenic ZEB2 variants have been reported for Chinese individuals ( Balasubramaniam et al, 2010 ; Jiang et al, 2016 ; Hu et al, 2018 ; Wang et al, 2019 ; Ho et al, 2020 ; Hu et al, 2020 ; Ma et al, 2020 ; Wu et al, 2020 ; Zou et al, 2020 ; Wei et al, 2021 ; Zhang et al, 2021 ). Furthermore, phenotypic differences between Chinese and Caucasian MWS individuals have been less delineated.…”

Clinical characteristics and novel ZEB2 gene mutation analysis of three Chinese patients with Mowat-Wilson syndrome

“…Due to the diversity of clinical phenotypes, MWS is di cult to be diagnosed clinically. Currently, more than 300 MWS patients have been reported [11][12][13] , and more than 280 ZEB2 variants have been found. However, only 35 cases of MWS and 25 pathogenic ZEB2 variants were reported in China [11,[15][16][17][18] .…”

“…It has been reported that the incidence of the disease is about 1:50, 000 to 1:70, 000 [10] . By reviewing the literature, it can be found that about 300 MWS patients have been reported, and about 280 ZEB2 variants have been found (Human Gene Mutation Database) [11][12][13][14] . 35 cases of MWS and 25 pathogenic ZEB2 variants have been reported in China [11,[15][16][17][18] .…”

Mowat–Wilson Syndrome: Case Report and Review of ZEB2 Gene Variant Types, Protein Defects and Molecular Interactions

“…Protein domain regions coded by exons are represented based on codon location within the domains (e.g., exon 9 codes for C-ZFa and exon 10 codes for C-ZFb). References are listed in brackets [ 6 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”