Case report of early-onset epileptic encephalopathy caused by compound heterozygous mutation of the WWOX gene / 中华实用儿科临床杂志

Clinical data of a case with early-onset epileptic encephalopathy admitted in the Department of Neuroendocrinology, Jinan Children′s Hospital in April 2020 were retrospectively analyzed.A 1-month-old male patient was hospitalized for convulsion for 4 days.The child had repeated seizures in the form of tonic and tonic-spasm seizures, accompanied by feeding difficulties, slow weight gain, and overall developmental delay.Electroencephalogram showed multifocal discharge, atypical hypsarrhythmia, and brain magnetic resonance imaging showed delayed myelination.The whole exome sequencing showed compound heterozygous mutation of the WWOX gene.Topiramate, Levetiracetam and Valporate were ineffective to this case.Genetic testing should be performed timely in patients with early-onset epileptic encephalopathy and overall developmental delay to make a clear etiology and prognosis, thus guiding prenatal diagnostics and genetic counseling.

Deletion and Mutation of WWOX Exons 6-8 in Human Non-small Cell Lung Cancer / 华中科技大学学报（医学）（英德文版）

To examine the deletion and point mutation of WWOX (WW domain containing oxidoreductase) exons 6-8 in human non-small cell lung cancer and their possible relationship with pathological stages, tumor tissues and the corresponding normal tissues were obtained from 44 Chinese patients who had undergone surgery for non-small cell lung cancer. RNA was extracted from each sample and deletion and mutation of WWOX exons 6-8 were analyzed by RT-PCR and DNA sequencing. Our results showed that 28 of 44 (63.6 %) lung cancer samples showed loss of WWOX exons 6-8 transcript and the deletion was detected in only 3 of 44 (6.8 %) corresponding adjacent normal tissues (P＜0.05). The transcript sequencing analyses of the 16 lung cancer samples without transcript loss of WWOX exons 6-8 revealed no difference from the sequence of GenBank. Moreover, the deletion of WWOX exons 6-8 was significantly higher in the smokers when compared with the non-smokers. It is also higher in the men and squamous carcinomas than in women and adenocarcinomas (P＜0.05). The deletion, however, was not found to be associated with pathological stages of the tumors. Our study documented a high incidence of deletion of WWOX exons 6-8 in non-small cell lung cancer in Chinese patients and suggested that the frequent loss of WWOX exons 6-8 might play an important role in the tumorigenesis of non-small cell lung cancer in Chinese. WWOX exons 6-8 may serves as a candidate molecular target of smoking carcinogenesis, and point mutation is not a predominant way of alteration of WWOX exons 6-8.

WWOX gene expression in non-small cell lung cancer and its clinical significance / 西安交通大学学报(医学版)

Objective To study the expression of WWOX gene in non-small cell lung cancer and its significance. Methods WWOX protein expression was evaluated by immunohistochemistry in 81 NSCLC patients(50 squamous cell carcinomas,31 adenocarcinomas and 20 adjacent normal lung tissues),and correlation with histopathologic(histotype,grade,tumor-node-metastasis,stage) and clinical characteristics was studied. Results WWOX expression was absent/reduced in 72.8% of NSCLC,whereas it was normal in 80.0% of adjacent normal lung tissues.WWOX expression was strongly associated with tumor histology and histologic grade(P

A study on expression changes of a tumor suppressor WWOX in human lung adenocarcinoma cell line A549 / 中国癌症杂志

Purpose:To detect the abnormalities of WWOX(WW domain containing oxidoreductase) gene in human lung adenocarcinoma cell line A549. Methods:Deletion of WWOX exons 6-8 transcript was analyzed by reverse transcriptase-PCR technology; loss of heterozygosity (LOH) of WWOX gene was analyzed by PCR-based assays for dinucleotide repeat polymorphisms technology. Aberrant expression of WWOX protein was analyzed by western blot. Results:A549 cells samples showed loss of WWOX exons 6-8 transcript.This deletion was not detected in normal primary cultured human bronchial epithelial cells samples.Three microsatellites(D16S3029、D16S3096、D16S504)did not have LOH in the normal primary cultured human bronchial epithelial cells samples, but D16S2029 and D16S3096 were all found to have LOH in A549 Cells samples. We further observed that expression of WWOX protein was significantly lower in A549 cell samples compared to the normal primary cultured human bronchial epithelial cells samples. Conclusions:WWOX gene may be important during tumorigenesis in lung adenocarcinoma cancer.Deletion of exons 6-8,LOH and aberrant expression of protein are all modes of WWOX gene inactivity in lung adenocarcinoma cancer.