Impaired Spermatogenesis due to Small Supernumerary Marker Chromosomes: The Reason for Infertility Is Only Reliably Ascertainable by Cytogenetics.

Infertile male with small supernumerary marker chromosomes (sSMCs) were studied. Overall, 37 own patients and 166 cases from the literature were included. sSMCs of our own cases were characterized by multicolor-FISH probe sets. Available clinical data of the infertile males were also evaluated, and meta-analysis on suitability of molecular karyotyping for sSMC characterization was done. As a result, sSMCs can be optimally characterized by single-cell directed (molecular) cytogenetics. In infertile males, sSMCs derive predominantly from one of the acrocentric chromosomes, mainly chromosomes 15, 14, and 22. Interestingly, altered spermiograms were found in 62% of the males with an sSMC, while the remainder cases had infertility in connection with recurrent spontaneous abortions. Meta-analysis for detectability of sSMCs by aCGH revealed that 81-87% of the cases would have not been picked up by exclusive use of that approach. Thus, as impaired spermatogenesis is known to be indicative for gross chromosomal anomalies in infertile male patients, it can be concluded from this study that the presence of sSMCs also needs to be considered. However, sSMCs can only be reliably detected by standard karyotyping and not by modern high throughput approaches like aCGH and next-generation sequencing.

Unusual de novo Partial Trisomy 17p12p11.2 due to Unbalanced Insertion into 5p13.1 in a Severely Affected Boy.

Gain of copy numbers can be due to different chromosomal rearrangements such as direct or indirect duplications, translocations, small supernumerary marker chromosomes, or insertions. In a 3-year-old boy with dysmorphic features and developmental delay, chromosome analyses revealed a derivative chromosome 5. Microdissection and reverse fluorescence in situ hybridization identified the in 5p13.1 inserted part as 17p12-p11.2 material. Thus the patient suffered from a rare combination of genomic disorder, that is, Charcot-Marie-Tooth disease type 1A and Potocki-Lupski syndrome. Parental studies indicated that the abnormality was de novo in origin. As the question how this rearrangement arose cannot be answered conclusively, formal genetic counseling is warranted, which includes a discussion regarding the possibility of gonadal mosaicism. In conclusion, this case highlights that chromosome 17p is genetically relatively instable, and thus it can lead to rare chromosomal conditions.