Whole-exome sequencing identifies novel homozygous mutation in NPAS2 in family with nonobstructive azoospermia

被引:52
|
作者
Ramasamy, Ranjith [1 ,2 ]
Bakircioglu, M. Emre
Cengiz, Cenk [1 ,2 ]
Karaca, Ender [3 ]
Scovell, Jason [1 ]
Jhangiani, Shalini N. [3 ]
Akdemir, Zeynep C. [3 ]
Bainbridge, Matthew [4 ]
Yu, Yao [5 ]
Huff, Chad [5 ]
Gibbs, Richard A. [3 ,6 ]
Lupski, James R. [3 ,6 ,7 ]
Lamb, Dolores J. [1 ,2 ]
机构
[1] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA
[2] Baylor Coll Med, Ctr Reprod Med, Houston, TX 77030 USA
[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[4] Codified Genom, Houston, TX USA
[5] Univ Texas Houston, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA
[6] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA
[7] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
Circadian rhythm; consanguineous; genome; male infertility; spermatogenesis; MISSENSE MUTATIONS; CLOCK;
D O I
10.1016/j.fertnstert.2015.04.001
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Objective: To investigate the genetic cause of nonobstructive azoospermia (NOA) in a consanguineous Turkish family through homozygosity mapping followed by targeted exon/whole-exome sequencing to identify genetic variations. Design: Whole-exome sequencing (WES). Setting: Research laboratory. Patient(s): Two siblings in a consanguineous family with NOA. Intervention(s): Validating all variants passing filter criteria with Sanger sequencing to confirm familial segregation and absence in the control population. Main Outcome Measure(s): Discovery of a mutation that could potentially cause NOA. Result(s): A novel nonsynonymous mutation in the neuronal PAS-2 domain (NPAS2) was identified in a consanguineous family from Turkey. This mutation in exon 14 (chr2: 101592000 C>G) of NPAS2 is likely a disease-causing mutation as it is predicted to be damaging, it is a novel variant, and it segregates with the disease. Family segregation of the variants showed the presence of the homozygous mutation in the three brothers with NOA and a heterozygous mutation in the mother as well as one brother and one sister who were both fertile. The mutation is not found in the single-nucleotide polymorphism database, the 1000 Genomes Project, the Baylor College of Medicine cohort of 500 Turkish patients (not a population-specific polymorphism), or the matching 50 fertile controls. Conclusion(s): With the use of WES we identified a novel homozygous mutation in NPAS2 as a likely disease-causing variant in a Turkish family diagnosed with NOA. Our data reinforce the clinical role of WES in the molecular diagnosis of highly heterogeneous genetic diseases for which conventional genetic approaches have previously failed to find a molecular diagnosis. (C) 2015 by American Society for Reproductive Medicine.
引用
收藏
页码:286 / 291
页数:6
相关论文
共 50 条
  • [1] WHOLE-EXOME SEQUENCING IDENTIFIES NOVEL HOMOZYGOUS MUTATION IN NPAS2 IN FAMILY WITH NONOBSTRUCTIVE AZOOSPERMIA
    Ramasamy, Ranjith
    Bakircioglu, Emre
    Cengiz, Cenk
    Karaca, Ender
    Scovell, Jason
    Bainbridge, Matthew
    Lupski, James
    Lamb, Dolores
    [J]. JOURNAL OF UROLOGY, 2015, 193 (04): : E985 - E986
  • [2] Whole-Exome Sequencing Identifies Homozygous GPR161 Mutation in a Family with Pituitary Stalk Interruption Syndrome
    Karaca, Ender
    Buyukkaya, Ramazan
    Pehlivan, Davut
    Charng, Wu-Lin
    Yaykasli, Kursat O.
    Bayram, Yavuz
    Gambin, Tomasz
    Withers, Marjorie
    Atik, Mehmed M.
    Arslanoglu, Ilknur
    Bolu, Semih
    Erdin, Serkan
    Buyukkaya, Ayla
    Yaykasli, Emine
    Jhangiani, Shalini N.
    Muzny, Donna M.
    Gibbs, Richard A.
    Lupski, James R.
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2015, 100 (01): : E140 - E147
  • [3] Whole-Exome Sequencing Identifies a Novel CPT2 Mutation in a Pedigree With Gout
    Guo, Yong
    Jin, Jing
    Zhou, Zhenni
    Chen, Yihui
    Sun, Li
    Zhang, Chunwu
    Xia, Xiaoru
    [J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2022, 10
  • [4] Whole-Exome Sequencing Identifies a Novel Mutation of Desmocollin 2 in a Chinese Family With Arrhythmogenic Right Ventricular Cardiomyopathy
    Liu, Ji-Shi
    Fan, Liang-Liang
    Li, Jing-Jing
    Xiang, Rong
    [J]. AMERICAN JOURNAL OF CARDIOLOGY, 2017, 119 (09): : 1485 - 1489
  • [5] Whole-Exome Sequencing Analysis of Idiopathic Hypogonadotropic Hypogonadism: Comparison of Varicocele and Nonobstructive Azoospermia
    Ma, Ziyang
    Dai, Yi
    Jin, Lei
    Luo, Yi
    Guo, Chen
    Qu, Rui
    He, Shengyin
    Liu, Yugao
    Xia, Yu
    Liu, Huan
    Kong, Lingnan
    Xu, Miaomiao
    Zhang, Lanlan
    Zhao, Yue
    Suliya, Yushanjiang
    Yuan, Dongzhi
    Yang, Luo
    [J]. REPRODUCTIVE SCIENCES, 2024, 31 (01) : 222 - 238
  • [6] Whole-exome sequencing identified a novel mutation in CHM of a Chinese family
    Tang, Hui
    Mao, Jun
    Xiang, Jingjing
    Liu, Minjuan
    Li, Haibo
    Wang, Ting
    [J]. JOURNAL OF GENETICS, 2021, 100 (02)
  • [7] Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing
    Liu, Yu-Jun
    Zhuang, Xin-Jie
    An, Jian-Ting
    Jiang, Hui
    Li, Rong
    Qiao, Jie
    Yan, Li-Ying
    Zhi, Xu
    [J]. ASIAN JOURNAL OF ANDROLOGY, 2023, 25 (01) : 66 - 72
  • [8] Whole-Exome Sequencing Analysis of Idiopathic Hypogonadotropic Hypogonadism: Comparison of Varicocele and Nonobstructive Azoospermia
    Ziyang Ma
    Yi Dai
    Lei Jin
    Yi Luo
    Chen Guo
    Rui Qu
    Shengyin He
    Yugao Liu
    Yu Xia
    Huan Liu
    Lingnan Kong
    Miaomiao Xu
    Lanlan Zhang
    Yue Zhao
    Yushanjiang Suliya
    Dongzhi Yuan
    Luo Yang
    [J]. Reproductive Sciences, 2024, 31 : 222 - 238
  • [9] Whole-exome sequencing identified a novel mutation in CHM of a Chinese family
    Hui Tang
    Jun Mao
    Jingjing Xiang
    Minjuan Liu
    Haibo Li
    Ting Wang
    [J]. Journal of Genetics, 2021, 100
  • [10] Whole-exome deep sequencing identifies a novel causative mutation in primary immunodeficiency
    McDonald, D.
    Morgan, N.
    Griffin, H.
    Dang, T. Singh
    Grainger, A.
    Reynard, L.
    Loughlin, J.
    Santibanez-Koref, M.
    Hambleton, S.
    [J]. IMMUNOLOGY, 2011, 135 : 43 - 43