Unbalanced X;9 translocation in an infertile male with de novo duplication Xp22.31p22.33

Abstract

Purpose Male carriers of an X-autosome translocation are generally infertile, regardless of the position of the breakpoint on the X chromosome while the pathogenicity of Xp22.3 subtelomeric duplications is under debate. To shed light into this controversy, we present a rare case, of an azoospermic male with no other significant clinical findings, in whom classical cytogenetics revealed additional unbalanced chromosomal material, at the telomere of the long arm of one homolog of chromosome 9. Methods In peripheral blood specimens of the index case and his parents, we performed GBanding, Inverted-DAPI Banding, AgNOR staining, Telomere specific Fluorescence in Situ Hybridization (FISH), Molecular karyotyping by Multi-color FISH, whole genome SNP microarrays, sub-telomeric MLPA, and transcription analysis of the expression of KAL1 gene by RT-PCR. Results Multi-color FISH revealed an unbalanced translocation involving the short arm of chromosome X. SNP microarray analysis combined to classical cytogenetics and MLPA demonstrated a de novo 8.796 Mb duplication of Xp22.31-p22.33. Compared to three control specimens, the patient presented significantly elevated expression levels of KAL1 mRNA in peripheral blood, suggesting transcriptional functionality of the duplicated segment. Conclusions The duplicated segment contains the pseudo-autosomal region PAR1 and more than 30 genes including SHOX, ARSE, STS, KAL1, and FAM9A and is not listed as polymorphic. Our data advocate that duplications of the Xp22.3 region may not be associated with a clinical consequence.

Reciprocal translocation and Robertsonian translocation in relation to semen parameters: A retrospective study and systematic review

“…The relationship between structural chromosomal aberrations and semen is significant in different individuals. Male carriers of a balanced X‐autosome or Y‐autosome translocations are almost invariably infertile due to severe defects in spermatogenesis that result in severe oligoasthenospermia or azoospermia (Kim et al., 2012; Roumelioti et al., 2019). Previous studies have reported conflicting results regarding the relationships between reciprocal translocation, Robertsonian translocation and semen parameters for autosomal translocations (Mayeur et al., 2019; Pastuszek et al., 2015; Vozdova et al., 2013).…”

A familial analysis of two brothers with azoospermia caused by maternal 46,Y, t(X; 1) (q28; q21) chromosomal abnormality

“…The mosaic karyotype 45,X/46,X,i(Y) (q10)/46,XX/47,XX,i(Y)(q10) reportedly contributed to azoospermia in a 38-year-old infertile man (Barnabas et al, 2018). A de novo 8.796 Mb duplication of Xp22.31-p22.33 was detected in an infertile man harbouring an X; 9 translocation (Roumelioti et al, 2019).…”