Molecular cytogenetic characterization of small supernumerary marker 15 in infertile male: A case report

Abstract

Small supernumerary marker chromosomes (sSMCs) are defined as structurally abnormal chromosomes that may be detected pre-or postnataly in patients with developmental and/or mental retardation or infertility. sSMC on chromosome 15 accounts for the highest proportion of all sSMCs and may be detected in subfertile individuals. The present study reports the case of a male patient with oligoasthenoteratozoospermia and an sSMC. The sSMC was identified and characterized according to G-banding analysis, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) analysis. Chromosomal karyotype analysis suggested that the patient presented with 47,XY,+mar. CMA was used to characterize the sSMC, which revealed a 0.44-Mb microduplication in 6q25.3q26. Subsequently, FISH using centromere-specific probes for chromosomes 13/21, 14/22 and 15 was applied to identify the origin of the sSMC, which was finally determined to be inverted duplicated(15) (q11.2). It was hypothesized that heterochromatin in the sSMC is responsible for the patient's fertility problem. The presence of heterochromatin may disrupt regular meiosis, thereby affecting normal spermatogenesis. Impaired spermatogenesis in infertile males with an sSMC derived from chromosome 15 was also reviewed by searching published literature and the sSMC database (http://ssmc-tl.com/sSMC.html). For patients with low sperm parameters and complete absence of spermatozoa in the ejaculate, including infertile males with an sSMC with spermatozoa, intracytoplasmic sperm injection is considered as an effective assisted reproductive technique. It may be concluded that molecular cytogenetic techniques are critical tools for delineating sSMCs in infertile males and may be beneficial in identifying sSMC carriers to ensure they receive clinical genetic counseling.

Meiotic Segregation of an Isodicentric Derived from Chromosome 15 in Sperm of a Patient with Mosaic Karyotype: Case Report and Review of the Literature

“…Armanet et al [2015] found that 72% of sSMCs detected in association with infertility are derived from acrocentric chromosomes [Armanet et al, 2015]. Some hypotheses have been advanced to explain the cause of infertility in these men, such as the presence of an interchromosomal effect [Guediche et al, 2012;Armanet et al, 2015] and/or an association between the NOR and meiotic abnormalities [Sun et al, 2020].…”

The Role of Genetics and Oxidative Stress in the Etiology of Male Infertility—A Unifying Hypothesis?

“…Catsper is also located in this area of the genome and defects in this critical sperm component are also associated with male infertility (210). The presence of small supernumerary marker chromosomes (sSMCs) is similarly associated with severe male infertility involving oligoasthenoteratozoospermia and most commonly involves chromosome 15 (211). Large deletions on chromosome 15 including the Catsper gene, and another gene also associated with spermatozoa, STRC (stereocilin), have also been linked to a rare condition characterized by male infertility and deafness (212).…”