P-239: NGS Mapping Breakpoints of a Familial Chromosome Insertion (18:7) (q22.1; q36.2 q21.11) to DPP6 and CACNA2D1 Genes in An Azoospermic Man

Background: Aberrant chromosomes can cause azoospermia but little is known about its molecular mechanism. Our aim is to explore any possible genetic defective to explain a given male infertility. Materials and Methods: An azoopsermic male was identified in a 23 years old male. G-banding and FISH confirmed the karyotype as chromosome insertion (18:7) (q22.1; q36.2q21.11). NGS was performed to analyze the breakage pints and around sequences. Results: 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 100Kb, 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. Conclusion: This is the first report describing chromosome insertion inv ins (18; 7). Our NGS analysis showed that DPP6 and CACNA2D1 may attribute to azoospermia, and Alu-like sequences may mediate the chromosome insertion.