|Year : 2020 | Volume
| Issue : 2 | Page : 75-78
Presence of pericentric inversion in chromosome 9 in all family members
Anjali S Sabnis
Professor and Head, Department of Anatomy, MGM Medical College, Navi Mumbai, Maharashtra, India
|Date of Submission||01-Apr-2020|
|Date of Decision||17-May-2020|
|Date of Acceptance||28-May-2020|
|Date of Web Publication||10-Sep-2020|
Anjali S Sabnis
Department of Anatomy, 1st Floor, MGM Medical College, Kamothe, Near Mumbai–Pune Express Highway, Navi Mumbai - 410 209, Maharashtra
Source of Support: None, Conflict of Interest: None
Pericentric inversion is the most common type of inversion encountered in human beings. Although pericentric inversion in chromosome 9 is generally considered as normal variant without any phenotypic presentations, some conditions associated with it, like mental retardation. In the present case, we discuss a baby with mental retardation showing pericentric inversion of chromosome 9 and also parents showing the same type of inversion on chromosome 9 without any phenotypic presentations.
Keywords: Karyotyping, mental retardation, pericentric inversion
|How to cite this article:|
Sabnis AS. Presence of pericentric inversion in chromosome 9 in all family members. Natl J Clin Anat 2020;9:75-8
| Introduction|| |
Inversion is one of the structural aberrations of chromosome where the part of chromosome gets rearranged because of two breakpoints. If the two breakpoints are in p or q arm of chromosome and the broken part gets reinserted upside down in 180° rotation, then it is termed as paracentric inversion, and when two breakpoints involve centromere, then it is termed as pericentric inversion. The most common form of inversion which is encountered in the human chromosomes is a pericentric inversion of chromosome 9 (inv9), which occurs in 1%–1.65% of the general population. Pericentric inversion in the heterochromatic region of chromosome 9 has been recognized as a normal variant, generally without phenotypic effect. Wide literature search clarifies that inversion in chromosome 9 is observed in conditions such as mental retardation,, infertility,,,, recurrent abortions, congenital anomaly,, dysmorphic features, Down syndrome,, impaired growth, and sexual development. Among the nonacrocentric human chromosomes, chromosome 9 represents the highest degree of morphological variations.
In the present case, the indication for karyotyping was mentally challenged child who showed the presence of pericentric inversion in one chromosome 9. Parent's karyotyping was done to see whether there was inheritance or de novo inversion 9 in the child, but it was found that both parents had inversion 9 in one chromosome number 9. The present study aimed to evaluate the correlation of inversion 9 with mentally challenged child.
| Case Report|| |
- A 3-month-old mentally challenged male baby who was referred from MGM Hospital to the Cytogenetic Laboratory, Department of Anatomy, for karyotyping
- On examination, the height of the baby was 56 cm and the weight was 5 kg; social smile was absent; there were no eye-to-eye contact, presence of depressed nasal bridge and simian crease on the left hand, while the absence of simian crease on the right hand. Head circumference was 41 cm [Figure 1]
- Birth history – Full Term Normal Delivery, hospital delivery
- Karyotyping was done by using the peripheral blood with the process of planting, harvesting, banding, and analysis. G banding was done and analysis was done by using IKAROS imaging software (MetaSystems, Germany).
- Karyotyping of the child showed pericentric inversion in one chromosome 9 [Figure 2]
- Both the parents were phenotypically normal and did not have consanguineous marriage. Male child in the case did not have any sibling. Karyotyping in both the parents was strongly recommended to study inheritance of pericentric inversion in chromosome 9. The parent's cytogenetic analysis was done after the genetic counseling (pretest session) and after taking consent. It was found that both the parents showed pericentric inversion in chromosome 9 [Figure 2].
| Discussion|| |
Karyotyping plays an important role to find out the structural and numerical chromosomal aberrations in patients with infertility, recurrent abortions, mentally challenged, and developmental delay. Commonly seen is an inversion in chromosome where the rearrangement in the chromosome happens because of two breakpoints. Pericentric inversion of chromosome 9 is the most common inversion observed in the human chromosomes. An inversion does not usually have phenotypic effect in the majority of pericentric inversion heterozygote carriers, when it is a balanced rearrangement. On the other hand, inv (9) was seen in patients in which various congenital anomalies including polydactyly, clubfoot, microtia, deafness, asymmetric face, giant Meckel's diverticulum, duodenal diaphragm, small bowel malrotation, pulmonary stenosis, cardiomyopathy, arrhythmia, and intrauterine growth restriction. Apart from infertility-related problems, inv (9) has also been associated with problems such as psychiatric disorders, ectodermal dysplasia, and azoospermia.
Mechanism of inv (9) is a complicated process. It has been suggested that phenotypes of inv (9) may vary depending on the location of breakpoints. An effect is related to genetic material lost during re-joining process. Euchromatic sequences may be suppressed or deleted during the breakage–reunion process, which could cause abnormal development. The human chromosome 9 displays the highest degree of structural variability. Molecular studies suggest that the structural organization of chromosome 9 is apparently prone to breakage and may be associated with a higher incidence of pericentric inversions. Therefore, pericentric inv (9) is the most common and best-known chromosomal alteration in humans. Carriers of such inversion are at risk of producing abnormal gametes during meiosis that may lead to unbalanced offspring. During meiosis I, a loop will be formed in chromosome with inversion which can lead to produce a percentage of abnormal and unbalanced gametes. These gametes may show duplication of the region outside the inversion segment on one arm of the inverted chromosome and deletion of the terminal segment on the other arm and vice versa, ending up with duplicated/deficient recombinant chromosomes distal to breakpoints. Some authors have proposed that the inversion itself could interfere with the pairing of homologous chromosomes during meiosis; this mechanism of recombination aneusomy is well described in some types of pericentric inversions. Some authors believe that inv (9) can influence the pairing of other chromosomes because the unpaired segments of homologous chromatids can interfere with other bivalents as well.
Pericentric inversions of chromosome 9, inv (9) (p11q12)/inv (9) (p11q13), are such common occurrences that a cytogeneticist would consider it as normal variants, and since most cytogeneticists believe inv (9) to be a simple heteromorphism, the clinical importance of any individual inv (9) in a specific clinical pathology may be challenging to determine. Inversion of chromosome 9 appears to have no phenotypic or clinical adverse effects or any apparent association with infertility problems. Inversion can be observed in 1%–3% of the general population, although the exact magnitude of the phenomenon is still unclear.,,,,
In the present case, parents were phenotypically normal with pericentric inv (9) and their son was mentally challenged with pericentric inv (9). Presence of pericentric inv (9) in all the family members is a rare phenomenon. The reasoning for mental retardation can be explained by two different ways. First reasoning for mental retardation is that pericentric inv (9) which could have been inherited from either parent in the child may not be a causative factor for mentally challenged status as the parents were phenotypically normal. Other reasoning for mental retardation is that there can be possibility that child may have had de novo pericentric inv (9) and not inherited pericentric inv (9) from either parent. Thus, pericentric inv (9) may not be causing harm in the present case as there may not be loss of genetic material.
Cytogenetic study with G banding is not sufficient to find out the cause of mentally challenged status of the child. Molecular cytogenetic approach such as fluorescent in situ hybridization (FISH) will be helpful to evaluate for mentally challenged status of the child.
| Conclusion|| |
Application of molecular study is required to confirm the cause of mental retardation.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]