Gene copy number variations in Asian patients with congenital bilateral absence of the vas deferens

Chia Huei Lee, Chien Chih Wu, Yi No Wu, Han-Sun Chiang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

BACKGROUND: Congenital bilateral absence of the vas deferens (CBAVD) is a distinct clinical entity accounting for ∼25% of obstructive azoospermia in infertile men. The association between CBAVD and mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles is well demonstrated in Caucasians, but the identity of CBAVD-susceptibility genes remains elusive in Asians. We investigate genomic copy number variations (CNVs) in a patient cohort of Taiwan. METHODS AND RESULTS: Genome-wide screening for genetic CNVs was conducted on eight individuals with CBAVD using array-based comparative genomic hybridization. One recurrent CNV was detected on 3q26.1 in five patients, and another was detected on a reproduction-related gene PANK2 in two patients. For the former, we further characterized the breakpoints in CBAVD and assessed the incidence in healthy individuals by tiling path arrays. The deletion in each patient was confirmed, and seven out of the eight controls were also affected. Examination of the homozygous loss of PANK2 by PCR in a larger cohort showed a homozygous deletion in only one of the 26 CBAVD males, and not in any of the 20 azoospermic patients without CBAVD, nor in any of the 16 control subjects. CONCLUSIONS: Our results suggest that 3q26.1 may not be a critical region for CBAVD. Additionally no strong association was found for PANK2 in this reproduction disorder. Other reproduction-related genes, such as PBX1, BRD3, COL18A1 and HMOX1, identified by this initial study may inspire further investigation.

Original languageEnglish
Pages (from-to)748-755
Number of pages8
JournalHuman Reproduction
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 2009

Fingerprint

Gene Dosage
Reproduction
Genes
Cystic Fibrosis Transmembrane Conductance Regulator
Azoospermia
Comparative Genomic Hybridization
Congenital bilateral aplasia of vas deferens
Genetic Testing
Taiwan
Alleles
Genome
Polymerase Chain Reaction
Incidence

Keywords

  • 3q26.1 microdeletion
  • Array-based comparative genomic hybridization
  • Congenital bilateral absence of the vas deferens
  • Copy number variations
  • Tiling path array

ASJC Scopus subject areas

  • Rehabilitation
  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Gene copy number variations in Asian patients with congenital bilateral absence of the vas deferens. / Lee, Chia Huei; Wu, Chien Chih; Wu, Yi No; Chiang, Han-Sun.

In: Human Reproduction, Vol. 24, No. 3, 03.2009, p. 748-755.

Research output: Contribution to journalArticle

Lee, Chia Huei ; Wu, Chien Chih ; Wu, Yi No ; Chiang, Han-Sun. / Gene copy number variations in Asian patients with congenital bilateral absence of the vas deferens. In: Human Reproduction. 2009 ; Vol. 24, No. 3. pp. 748-755.
@article{92e76b9e8f1940fe83a589b231a769d0,
title = "Gene copy number variations in Asian patients with congenital bilateral absence of the vas deferens",
abstract = "BACKGROUND: Congenital bilateral absence of the vas deferens (CBAVD) is a distinct clinical entity accounting for ∼25{\%} of obstructive azoospermia in infertile men. The association between CBAVD and mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles is well demonstrated in Caucasians, but the identity of CBAVD-susceptibility genes remains elusive in Asians. We investigate genomic copy number variations (CNVs) in a patient cohort of Taiwan. METHODS AND RESULTS: Genome-wide screening for genetic CNVs was conducted on eight individuals with CBAVD using array-based comparative genomic hybridization. One recurrent CNV was detected on 3q26.1 in five patients, and another was detected on a reproduction-related gene PANK2 in two patients. For the former, we further characterized the breakpoints in CBAVD and assessed the incidence in healthy individuals by tiling path arrays. The deletion in each patient was confirmed, and seven out of the eight controls were also affected. Examination of the homozygous loss of PANK2 by PCR in a larger cohort showed a homozygous deletion in only one of the 26 CBAVD males, and not in any of the 20 azoospermic patients without CBAVD, nor in any of the 16 control subjects. CONCLUSIONS: Our results suggest that 3q26.1 may not be a critical region for CBAVD. Additionally no strong association was found for PANK2 in this reproduction disorder. Other reproduction-related genes, such as PBX1, BRD3, COL18A1 and HMOX1, identified by this initial study may inspire further investigation.",
keywords = "3q26.1 microdeletion, Array-based comparative genomic hybridization, Congenital bilateral absence of the vas deferens, Copy number variations, Tiling path array",
author = "Lee, {Chia Huei} and Wu, {Chien Chih} and Wu, {Yi No} and Han-Sun Chiang",
year = "2009",
month = "3",
doi = "10.1093/humrep/den413",
language = "English",
volume = "24",
pages = "748--755",
journal = "Human Reproduction",
issn = "0268-1161",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Gene copy number variations in Asian patients with congenital bilateral absence of the vas deferens

AU - Lee, Chia Huei

AU - Wu, Chien Chih

AU - Wu, Yi No

AU - Chiang, Han-Sun

PY - 2009/3

Y1 - 2009/3

N2 - BACKGROUND: Congenital bilateral absence of the vas deferens (CBAVD) is a distinct clinical entity accounting for ∼25% of obstructive azoospermia in infertile men. The association between CBAVD and mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles is well demonstrated in Caucasians, but the identity of CBAVD-susceptibility genes remains elusive in Asians. We investigate genomic copy number variations (CNVs) in a patient cohort of Taiwan. METHODS AND RESULTS: Genome-wide screening for genetic CNVs was conducted on eight individuals with CBAVD using array-based comparative genomic hybridization. One recurrent CNV was detected on 3q26.1 in five patients, and another was detected on a reproduction-related gene PANK2 in two patients. For the former, we further characterized the breakpoints in CBAVD and assessed the incidence in healthy individuals by tiling path arrays. The deletion in each patient was confirmed, and seven out of the eight controls were also affected. Examination of the homozygous loss of PANK2 by PCR in a larger cohort showed a homozygous deletion in only one of the 26 CBAVD males, and not in any of the 20 azoospermic patients without CBAVD, nor in any of the 16 control subjects. CONCLUSIONS: Our results suggest that 3q26.1 may not be a critical region for CBAVD. Additionally no strong association was found for PANK2 in this reproduction disorder. Other reproduction-related genes, such as PBX1, BRD3, COL18A1 and HMOX1, identified by this initial study may inspire further investigation.

AB - BACKGROUND: Congenital bilateral absence of the vas deferens (CBAVD) is a distinct clinical entity accounting for ∼25% of obstructive azoospermia in infertile men. The association between CBAVD and mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles is well demonstrated in Caucasians, but the identity of CBAVD-susceptibility genes remains elusive in Asians. We investigate genomic copy number variations (CNVs) in a patient cohort of Taiwan. METHODS AND RESULTS: Genome-wide screening for genetic CNVs was conducted on eight individuals with CBAVD using array-based comparative genomic hybridization. One recurrent CNV was detected on 3q26.1 in five patients, and another was detected on a reproduction-related gene PANK2 in two patients. For the former, we further characterized the breakpoints in CBAVD and assessed the incidence in healthy individuals by tiling path arrays. The deletion in each patient was confirmed, and seven out of the eight controls were also affected. Examination of the homozygous loss of PANK2 by PCR in a larger cohort showed a homozygous deletion in only one of the 26 CBAVD males, and not in any of the 20 azoospermic patients without CBAVD, nor in any of the 16 control subjects. CONCLUSIONS: Our results suggest that 3q26.1 may not be a critical region for CBAVD. Additionally no strong association was found for PANK2 in this reproduction disorder. Other reproduction-related genes, such as PBX1, BRD3, COL18A1 and HMOX1, identified by this initial study may inspire further investigation.

KW - 3q26.1 microdeletion

KW - Array-based comparative genomic hybridization

KW - Congenital bilateral absence of the vas deferens

KW - Copy number variations

KW - Tiling path array

UR - http://www.scopus.com/inward/record.url?scp=61449114896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61449114896&partnerID=8YFLogxK

U2 - 10.1093/humrep/den413

DO - 10.1093/humrep/den413

M3 - Article

C2 - 19095672

AN - SCOPUS:61449114896

VL - 24

SP - 748

EP - 755

JO - Human Reproduction

JF - Human Reproduction

SN - 0268-1161

IS - 3

ER -