Research Papers:
Identification and functional analysis of a novel LHX1 mutation associated with congenital absence of the uterus and vagina
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Abstract
Wei Zhang1,2,3,*, Xueya Zhou4,5,*, Liyang Liu4, Ying Zhu1, Chunmei Liu6, Hong Pan3, Qiong Xing1, Jing Wang7, Xi Wang3, Xuegong Zhang4, Yunxia Cao1, Binbin Wang2,3
1Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China
2Graduate School, Peking Union Medical College, Beijing, China
3Center for Genetics, National Research Institute for Family Planning, Beijing, China
4MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic and Systems Biology, TNLIST/Department of Automation, Tsinghua University, Beijing, China
5Department of Psychiatry and Centre for Genomic Sciences, Li KaShing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
6Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, China
7Department of Medical Genetics, School of Basic Medical Sciences, Capital Medical University, Beijing, China
*These authors have contributed equally to this work
Correspondence to:
Binbin Wang, email: [email protected]
Yunxia Cao, email: [email protected]
Keywords: LHX1, congenital absence of the uterus and vagina, Müllerian duct abnormality, whole exome sequencing, transcriptional activity
Received: July 20, 2016 Accepted: October 22, 2016 Published: January 02, 2017
ABSTRACT
Congenital absence of the uterus and vagina (CAUV) is the most extreme female Müllerian duct abnormality. Several researches proposed that genetic factors contributed to this disorder, whereas the precise genetic mechanism is far from full elucidation. Here, utilizing whole-exome sequencing (WES), we identified one novel missense mutation in LHX1 (NM_005568: c.G1108A, p.A370T) in one of ten unrelated patients diagnosed with CAUV. This mutation was absent from public databases and our internal database. Through the luciferase reporter analysis, we found that the mutation could change the transcriptional activity of LHX1 and its effect on the regulation of the downstream target gene GSC, which might be associated with urogenital system development. In short, we concluded that the LHX1 may be a pathogenic gene of CAUV. Our results demonstrate the power of whole exome sequencing and gene prioritization approach as diagnostic tools in clinical practice that help make genetic diagnosis of CAUV.
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