The chromosomal polymorphism defined by variations of some chromosomal regions of a person (the constitutive heterochromatin and the short arms of the acrocentric chromosomes (13 to 15 and 21 - 22)) sometimes highlighted problems with regard to their safety and their pathogenicity. Polymorphisms are usually found in the same family and transmitted in the dominant Mendelian. Chromosome 9 inversion is a frequent phenomenon that some cytogeneticists consider as a variant of normal. Despite its classification as a minor chromosome rearrangement which does not correspond to abnormal phenotypes, many reports have raised conflicting opinions as well, and its complete safety is controversial. 27 cases of inversion of chromosome 9 were identified in our laboratory. The main indications for karyotype of the case of inv (9) were congenital cardiopathy (18.5%), sex development disorders of (18.5%), down syndrome (18.5%), and infertility (14.8%). This study stood out the observations of many authors who highlighted the involvement of inv (9) in the genesis of several pathologies.
Constitutional chromosomal abnormalities are an important cause of miscarriage, infertility, congenital anomalies, and mental retardation in humans. Constitutional chromosomal abnormalities include numeral chromosomal aberrations that cause aneuploidy and structural chromosomal aberrations such as translocations, inversions, deletions, and duplications [
In order to study the frequency and the phenotype associated with inv (9), we reported 27 cases, in the Laboratory of Histology-Biology of Reproduction, Cytogenetics and Medical Genetics of Cotonou, Benin.
It was a retrospective study including cases of inv (9) at the Cytogenetics Laboratory of Cotonou from January 1, 2014 to June 30, 2020. The data were collected in the laboratory’s registers. As they were routine patients, a written approval was not obtained from the ethical committee of Faculty of Health Science of Cotonou.
The study population includes all the patients admitted to laboratory during the study period. The karyotype was performed in a G band. The culture tubes were incubated for 72 hours at 37˚C, CO2 5%. The culture was stopped at the 70th hour by adding 50 μl of colcemide (SigmaR). Hypotonic treatment of the cells with KCl (0.075 M) followed by fixation in ethanol/glacial acetic acid (3:1 vol; vol). A concentrated suspension of cells was placed on slides and dried, for 25 minutes. The chromosomes were obtained by digestion in a trypsin bath and stained using 2% Giemsa solution. They were then dried and examined under the microscope using the programmed image analyzer (Cytovision 7.3.1). The metaphases were captured using a microscope and interpreted in accordance with the international system of Human Cytogenetic Nomenclature (ISCN).
Over 5-year, 1049 karyotypes were performed. Inv (9) was observed in 27 cases (2.57 %). The inv (9) was predominant in male subjects with a sex ratio of 1.17.The average age of the patients was 12.65 years with extremes from 03 months to 39 years. The majority (46.15%) of our patients were between 0 and 1 year of age.
The type of inversion observed was q11-q22.3. We also observed a case with mosaicism 46, XX (85%)/46, XX, inv (9), five cases associated with Down’s syndrome and one case with duplication of chromosome 9 (46, XY, inv (9), dup (q13 P11). Figures 1-4 show metaphasic finding of some genotypics aspects of inv chr (9).
| Case | Sex | Age (years) | Clinical aspects | Genotypics forms |
|---|---|---|---|---|
| Case 1 | F | 0.25 (3 months) | Congenital Cardiopathy | 46, XX, inv (9) |
| Case 2 | F | 0.33 (4 months) | Developpement sexual disorders (DSD) | 46, XX, inv (9) |
| Case 3 | M | 0.75 (9 months) | Congenital Cardiopathy | 46, XY, inv (9) |
| Case 4 | M | 31 | Infertility (severe oligospermia) | 46, XY, inv (9) |
| Case 5 | M | 0.75 (9 months) | Developpement sexual disorders (DSD) | 46, XY, inv (9) |
| Case 6 | F | 35 | Infertility (primary amenorrhea) | 46, XX, inv (9) |
| Case 7 | M | 0.75 (9 months) | Facial dysmorphia | 46, XY, inv (9) |
| Case 8 | F | 1 | Congenital Cardiopathy | 46, XX, inv (9) |
| Case 9 | M | 38 | Developpement sexual disorders (DSD) | 46, XY, inv (9) |
| Case 10 | M | 15 | Facial dysmorphia | 46, XY, inv (9) |
| Case 11 | M | 39 | Suspicion Klinefelter’s syndrome | 46, XY, inv (9) |
| Case 12 | F | 0.60 (8 months) | Congenital Cardiopathy | 46, XX (85%)/46, XX, inv (9) (15%) |
| Case 13 | F | 2 | Down syndrome | 47, XX, +21, inv (9) |
| Case 14 | F | 14 | Developpement sexual disorders (DSD) | 46, XX, inv (9) |
| Case 15 | M | 0.75 (9 months) | Down syndrome | 47, XY, + 21, inv (9) |
| Case 16 | M | 4 | Congenital Cardiopathy | 46, XY, inv (9) |
| Case 17 | M | 0.58 (7months) | Down syndrome | 46, XY, +21, inv (9) |
| Case 18 | M | 10 | Developpement sexual disorders (DSD) | 46, XY, inv (9) |
| Case 19 | M | 0.75 (9 months) | hypotrophy | 46, XY, inv (9) |
| Case 20 | M | 1.83 (22 months) | Psychomotor retardation | 46, XY, inv (9) |
| Case 21 | M | 1.83 (22months) | Polymalformative syndrome | 47, XY, +13, inv (9) |
| Case 22 | M | 35 | recurrent abortions | 46, XY, inv (9) |
| Case 23 | M | 0.25 (3 months) | Down syndrome | 46, XY, +21, inv (9) |
| Case 24 | F | 0.33 (4 months) | Down syndrome | 46, XX, +21, inv (9) |
| Case 25 | M | 46 | Infertility (oligospermia) | 46, XY, inv (9) |
| Case 26 | M | 33 | Infertility (azoospermia hypogonadism) | 46, XY, inv (9) |
| Case 27 | M | 0.75 (9 months) | Hypotrophy | 46, XY, inv (9), dup (q13 P11) |
The inv (9) is a frequent phenomenon, sometimes considered to be a chromosomal polymorphism [
Inv (9), is one of the most common balanced structural chromosomal aberrations and occurs in approximatively 1% - 1.65% within a normal population. It’s important to notice that the prevalence of the inv chr9 in the general population varies with ethnicity [
In our study, the prevalence of inv Chr9 was 1.64%. Many other authors have reported the same observation in their studies with an incidence between 1 and 3% [
The human chromosome 9 displays the highest degree of structural variability [
Chr 9 pericentric inversions are very rare phenomena. In our series, 27 cases, the most common clinical sign were: heart disease, abnormalities in sexual development and infertility. In Korea, Seon-Yong Jeong et al. reported 8 patients with inv (9) presenting various congenital abnormalities, in particular: polydactyly, giant Meckel’s diverticulum, poor rotation of the small intestine, cardiomyopathy, pulmonary stenosis [
Here, we summarized the literature reviews of some clinical feature on inv (9) [
Inv (9) and heart disease
We described 5 cases in our series. Few cases of this association were reported. The gène CFA9 on chromosome 9 is a succeptibility gène involved in the congenital heart defect [
Inv (9) and Infertility
Inv (9) is considered to be a predisposing factor for infertility. Five cases were observed in our study (Oligospermia, azoospermia and primary amenorrhea). Literature has raised divergent views regarding its correlation with hypofertility, recurrent abortions, spermatogenesis disorders and/or unbalanced offspring [
Inv (9) and Disorders of Sex Development
Five cases of sex development disturbances were observed in our study. Cases of micropenis and hypospadias associated with inv (9) have been reported [
Inv 9 and Malignant Hematological Disease
The link between inv (9) and leukemia were frequently reported. Indeed, in a series of 3809 cases of patients with malignant hematological disease, Sang Guk Lee has recorded 586 malignant pathologies and 55 chromosome 9 reversals [
Inv (9) and psychiatic disorders
Though some authors in literature have mentioned association of inv (9) and psychiatric disorders [
Inv chr9 and prenatal pathology
Inv (9) is considered as a polymorphic variation and is one of the most common forms of autosomal inversion diagnosed prenatally in amniocytes. Yet its clinical significance remains uncertain. Most publications suggest that this finding is insignificant. However, some articles report on abnormal ultrasonic findings in association, such as hydramnios, anhydramnios, hydroureter, hydronephrosis, encephalocele, and prune belly syndromes [
This study reinforced the observations of several authors who underline the involvement of chromosome 9 inversion in occurring of various pathologies. Molecular cytogenetic examinations such as comparative genomic hybridization may prove essential to establish the relationship between the genetic abnormalities of this condition and the consequences on the phenotype of the subject.
The authors declare no conflicts of interest regarding the publication of this paper.
Azonbakin, S., Ouedraogo, A., Ouedraogo, A., Sewadouno, D., Agbanlinsou, A., Goussanou, Y., Adjagba, M., Alao, J. and Laleye, A. (2021) Chromosome Polymorphism and Human Pathology: About 27 Cases of Chromosome 9 Inversion in the Beninese Population. Open Journal of Genetics, 11, 23-31. https://doi.org/10.4236/ojgen.2021.113003