Hypogonadotropic hypogonadism associated with another small supernumerary marker chromosome (sSMC) derived from chromosome 22, a case report

Abstract

The idiopathic hypogonadotropic hypogonadism (IHH) is portrayed as missing or fragmented pubescence, cryptorchidism, small penis, and infertility. Clinically it is characterized by the low level of sex steroids and gonadotropins, normal radiographic findings of the hypothalamic-pituitary areas, and normal baseline and reserve testing of the rest of the hypothalamic-pituitary axes. Delay puberty and infertility result from an abnormal pattern of episodic GnRH secretion. Mutation in a wide range of genes can clarify ~40% of the reasons for IHH, with the majority remaining hereditarily uncharacterized. New and innovative molecular tools enhance our understanding of the molecular controls underlying pubertal development. In this report, we aim to present a 26-year-old male of IHH associated with a small supernumerary marker chromosome (sSMC) that originated from chromosome 22. The G-banding analysis revealed a karyotype of 47,XY,+mar. High-throughput DNA sequencing identified an 8.54 Mb duplication of 22q11.1-q11.23 encompassing all the region of 22q11 duplication syndrome. Pedigree analysis showed that his mother has carried a balanced reciprocal translocation between Chromosomes 22 and X[t(X;22)]. To the best of our knowledge, this is the second confirmed case of IHH with an sSMC deriving from chromosome 22. Based on our study, the duplicated chromosome fragment 22q11.1-q11.23 might be the reason for the phenotype of our case. Meanwhile, High-throughput DNA sequencing combined with cytogenetic analysis can provide a more accurate clinical diagnosis for patients carrying sSMCs.

Keywords: 22q11 duplication syndrome; 22q11.1-q11.23; Small supernumerary marker chromosome (sSMC); high-throughput DNA sequencing; hypogonadotropic hypogonadism (HH).

Figure 1

Metaphase karyotype of the patient in GTG banding displaying the detected small supernumerary marker chromosomes: 47,XY,+mar.

Figure 2

Result of chromosomal aneuploidy or a known pathogenic genomic copy number variation (CNVs) above 100 Kb: (A) genome-wide detection showed Genome copy number variation (CNVs) increased, originating from chromosome 22; (B) detection of chromosome 22 showed a 8.54 Mb Trisomy duplication in the 22q11.1–q11.23 region.

Figure 3

Metaphase karyotype of the patient’s mother in GTG banding displaying balanced reciprocal translocation between Chromosome 22 and X Chromosome (arrow), i.e., 46,X,t(X;22)(p22.3;q11.2).