Azoospermia and ring chromosome 9--a case report.

Abstract

Ring chromosome abnormalities are rare abnormalities potentially involving any chromosome and the vast majority of previously reported cases were seen in patients with various congenital malformations and mental retardation. On the other hand, only few subjects carrying ring chromosomes and with normal phenotype have been described [1]. Until now only 30 cases of ring autosome 9 (r(9)) have been reported in the literature [2]. The prevalence of this pathology is 1 in 50,000 foetuses and in the majority of cases serious malformations were described [3]. The most typical ring formation occurs after terminal deletion and fusion of the p arm and the q arm and under this process genetic material can be lost [4]. The most common breakpoints are found between 9p24-p22 and 9q33-q34, but end-to-end fusion of palindromic telomere sequences have also been reported [5]. The Danish cytogenetic register, which contains data from all cytogenetic testing in Denmark from 1960 onwards (altogether 345,000 cases), has sparse information on two r(9) cases: a female, born in 1946, who died childless and a girl born 2008 for whom no more information is available. The most frequent malformations reported in connection with r(9) are related to the deleted regions of both arms and include growth and psychomotor retardation, facial dysmorphism, microcephaly, cardiac malformations, limb and skeletal anomalies [5]. Microdeletions in the telomeric region of the long arm of chromosome 9 were found in patients with Kleefstra syndrome [6, 7], whereas microdeletions of the telomeric end of the short arm may lead to 46,XY gonadal dysgenesis [2]. The literature regarding genital malformations in males with the presence of r(9) is very sparse; however the following malformations have previously been reported: cryptorchidism, hypospadias and micropenis [7]. Until now it is not clear whether the presence of r(9) affects spermatogenesis, as most cases have been described in young boys. Moreover, the literature is sparse regarding phenotypic details and sperm status. However azoospermia has previously been reported in males with other ring chromosomes, affecting chromosomes 12, 15, 21 and 22 [4, 8, 9]. The distal part of 9p is quite polymorphic and larger deletions of this region are often sporadic, combined with head/facial malformations like trigonocephaly, long philtrum, hypertelorism and micrognatia [2]. However, different gonadal disorders like complete gonadal dysgenesis, ovotestis, cryptorchidism and/or hypoplastic testes have also been described and typically these disorders were caused by deletions of three DMRT genes (DMRT1, DMRT2 and DMRT3) on the 9p24 region, with DMRT1 being the prime candidate [10]. These genes are involved in downstream pathways of sex determination; however the exact molecular mechanism is unclear. The present case describes an azoospermic male with r(9) and this case further highlight that autosomal ring chromosomes can be involved in male infertility.