• PMID: 24937803
• Gene Name: CACNA2D1
• Condition: Azoospermia, Recurrent miscarriages
• Association: The insertional translocation is confirmed with FISH and the Y-chromosome microdeletions were excluded by genetic testing. This is the first report describing chromosome insertion inv ins (18,7) and attributes DPP6 and CACNA2D1 to azoospermia.
• Mutation: 46, XY, inv ins(18,7) (q22.1; q36.2q21.11)
• Population size: 2
• Population details: 2 (1 azoospermia, 1 recurrent miscarriages)
• Sex: Male, female
• Infertility type: Male infertility, Female infertility
• Associated genes: DPP6, CACNA2D1
• Other associated phenotypes: Azoospermia, Recurrent miscarriages

Mapping breakpoints of a familial chromosome insertion (18,7) (q22.1; q36.2q21.11) to DPP6 and CACNA2D1 genes in an azoospermic male

Li L, Chen H, Yin C, Yang C, Wang B, Zheng S, Zhang J, Fan W.

It is widely accepted that the incidence of chromosomal aberration is 10-15.2% in the azoospermic male; however, the exact genetic damages are currently unknown for more than 40% of azoospermia. To elucidate the causative gene defects, we used the next generation sequencing (NGS) to map the breakpoints of a chromosome insertion from an azoospermic male who carries a balanced, maternally inherited karyotype 46, XY, inv ins (18,7) (q22.1; q36.2q21.11). The analysis revealed that the breakage in chromosome 7 disrupts two genes, dipeptidyl aminopeptidase-like protein 6 (DPP6) and contactin-associated protein-like 2 (CACNA2D1), the former participates in regulation of voltage-gated potassium channels, and the latter is one of the components in voltage-gated calcium channels. The deletion and duplication were not identified equal or beyond 100 kb, but 4 homologous DNA elements were verified proximal to the breakpoints. One of the proband's sisters inherited the same aberrant karyotype and experienced recurrent miscarriages and consecutive fetus death, while in contrast, another sister with a normal karyotype experienced normal labor and gave birth to healthy babies. The insertional translocation is confirmed with FISH and the Y-chromosome microdeletions were excluded by genetic testing. This is the first report describing chromosome insertion inv ins (18,7) and attributes DPP6 and CACNA2D1 to azoospermia. CI - Copyright © 2014 Elsevier B.V. All rights reserved. FAU - Li, Lin AU - Li L AD - Institute of Medical Genetics, Linyi People's Hospital, Shandong 276003, China. FAU - Chen, Haixiao AU - Chen H AD - BGI, 11-2 Building, Northern Industry District, Shenzhen 518083, China. FAU - Yin, Chenxing AU - Yin C AD - Key Laboratory of Medicinal Chemistry and Molecular Diagnosis, Hebei University School of Life Sciences, Baoding, Hebei 071002, China. FAU - Yang, Chuanchun AU - Yang C AD - BGI, 11-2 Building, Northern Industry District, Shenzhen 518083, China. FAU - Wang, Bei AU - Wang B AD - Key Laboratory of Medicinal Chemistry and Molecular Diagnosis, Hebei University School of Life Sciences, Baoding, Hebei 071002, China. FAU - Zheng, Shuqi AU - Zheng S AD - Institute of Medical Genetics, Linyi People's Hospital, Shandong 276003, China. FAU - Zhang, Jixia AU - Zhang J AD - Institute of Medical Genetics, Linyi People's Hospital, Shandong 276003, China.