New biallelic mutations in WEE2: expanding the spectrum of mutations that cause fertilization failure or poor fertilization.
Fertil Steril
; 111(3): 510-518, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30827523
ABSTRACT
OBJECTIVE:
To investigate the genetic cause of fertilization failure or poor fertilization.DESIGN:
Genetic analysis.SETTING:
University-affiliated center. PATIENT(S) Twenty-four Chinese women who underwent assisted reproductive technology (ART) and had repeated fertilization failure or poor fertilization. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Twenty-four affected patients were subjected to whole-exome sequencing and candidate mutations were validated by Sanger sequencing. Single-cell reverse transcription was used to analyze the functional characterization of the splice-site mutation in vivo. Evolutionary conservation and molecular modeling analyses were used to predict the impact of missense mutations on secondary protein structure. Immunofluorescence was used to analyze the protein levels of WEE2 and phosphorylated CDC2. RESULT(S) Biallelic mutations in WEE2 were identified in 5 of 24 (20.8%) Chinese patients with fertilization failure or poor fertilization. Among these individuals we found a novel splice-site mutation, two novel missense mutations, and a previously reported frame-shift mutation. Splicing mutation c.1136-2A>G of WEE2 caused an alteration of the reading frame and introduced a premature stop codon (p.Gly379Glufs*6/p.Asp380Leufs*39). The missense mutations c.585G>C (p.Lys195Asn) and c.1228C>T (p.Arg410Trp) produced obvious changes in secondary protein structures. Immunostaining indicated that mutated WEE2 resulted in the loss of phosphorylated CDC2. The phenotypes of women carrying WEE2 mutations exhibited slight variability, from total fertilization failure to poor fertilization. CONCLUSION(S) Novel mutations in the known causative gene WEE2 were identified in 5 of 24 women with fertilization failure or poor fertilization, indicating a high prevalence of WEE2 mutations in Chinese women experiencing fertilization failure or poor fertilization.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
/
Proteínas de Ciclo Celular
/
Técnicas de Reprodução Assistida
/
Fertilidade
/
Infertilidade Feminina
/
Mutação
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Pregnancy
País/Região como assunto:
Asia
Idioma:
En
Revista:
Fertil Steril
Ano de publicação:
2019
Tipo de documento:
Article