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ORIGINAL ARTICLE
Year : 2007  |  Volume : 13  |  Issue : 1  |  Page : 26-29
 

Impact of pericentric inversion of Chromosome 9 [inv (9) (p11q12)] on infertility


1 Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
2 Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University; Department of Genetics, Royan Institute, Tehran, Iran
3 Department of Genetics, Royan Institute, Tehran, Iran

Correspondence Address:
Hossein Mozdarani
Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, P.O. Box 14115 - 111
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-6866.32031

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   Abstract 

Background : One of the frequent occurrences in chromosome rearrangements is pericentric inversion of the Chromosome 9; inv (9) (p11q12), which is consider to be the variant of normal karyotype. Although it seems not to correlate with abnormal phenotypes, there have been many controversial reports indicating that it may lead to abnormal clinical conditions such as infertility. The incidence is found to be about 1.98% in the general population.
Materials and Methods :
We investigated the karyotypes of 300 infertile couples (600 individuals) being referred to our infertility clinic using standard GTG banding for karyotype preparation.
Results : The chromosomal analysis revealed a total of 15 (2.5%) inversions, among these, 14 male patients were inversion 9 carriers (4.69%) while one female patient was affected (0.33%). The incidence of inversion 9 in male patients is significantly higher than that of normal population and even than that of female patients (P<0.05).
Conclusions : This result suggests that inversion 9 may often cause infertility in men due to spermatogenic disturbances, which are arisen by the loops or acentric fragments formed in meiosis.


Keywords: Infertility, inversion 9, Iranian population, metaphase analysis


How to cite this article:
Mozdarani H, Meybodi AM, Karimi H. Impact of pericentric inversion of Chromosome 9 [inv (9) (p11q12)] on infertility. Indian J Hum Genet 2007;13:26-9

How to cite this URL:
Mozdarani H, Meybodi AM, Karimi H. Impact of pericentric inversion of Chromosome 9 [inv (9) (p11q12)] on infertility. Indian J Hum Genet [serial online] 2007 [cited 2017 Mar 30];13:26-9. Available from: http://www.ijhg.com/text.asp?2007/13/1/26/32031



   Introduction Top


Pericentric inversions result from a two-break event in which there is a break in each arm including the centromere. [1] An inversion does not usually have phenotypic effect in the majority of pericentric inversion heterozygote carriers, when it is a balanced rearrangement. However, infertility, miscarriages and/or chromosomally unbalanced offspring can be observed in carriers of either type of inversions specially pericentric inversions. [2] Carriers of such inversions 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 the breakpoints. [3] The most common inversion seen in human chromosomes is a small pericentric inversion of Chromosome 9, with an overall incidence of 1.98%, especially in African-Americans. [4] According to different studies this inversion can also be seen in 1-3% of general population and the exact amount of this phenomenon is still unclear. [5],[6],[7],[8],[9] The human Chromosome 9 displays the highest degree of structural variability. [10] Review of literature showed that inversions of Chromosome 9 with different breakpoints could be the cause of different disturbances in carriers. Pericentric inversions of Chromosome 9, inv (9) (p11q12)/ inv (9) (p11q13), are such common occurrences that cytogeneticist would consider it as normal variants. Despite being categorized as minor chromosomal rearrangements, which does not correlate with abnormal phenotypes, many reports raised the association of these inversions with sub fertility, recurrent abortions and abnormal clinical phenotypes. [9] The present study aimed to evaluate the association between inversion 9 (p11q12) and infertility.


   Materials and Methods Top


The patient population consisted of those Iranian couples who attended the infertility clinic. A total of 601 patients with at least three years of infertility were examined. The age of the referred wives ranged from 21-38 years, while the age of the husbands ranged from 25-42 years.

Cytogenetic analysis was performed with GTG banding technique for their lymphocytes.

G-banded chromosomes from peripheral blood were prepared according to the modifications of Verma and Babu. [11] Whole complete blood cultures were set up in 10 ml culture tubes. The medium had the following composition: 100 ml RPMI medium (Sigma) supplemented with 20 ml fetal calf serum (Gibco BRL), 1.2 ml Glutamine (Sigma), 1 ml phytohaemagglutinine (Sigma) and penicillin streptomycin (Sigma) mix was added. Five to ten drops of heparinized blood were added to 5 ml of the complete media. Culture tubes were incubated for 72h in a slanting position at 37C. Colcemid (Sigma) was added at 4 g/ml to the cultures 2h before harvesting. Slides were prepared after 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 the cells was dropped on slides, which were dried on a slide warmer at 60C for a few seconds. G-banded chromosomes were obtained by keeping the slides in an oven at 55-60C then treating them with trypsin solution and stained in 4% Giemsa solution (Merck), dried and examined microscopically using the image analyzer programmed (Cytovision, version 2000, Applied Imaging). Metaphases were karyotyped and interpreted according to the international system for human cytogenetic nomenclature (ISCN). [12]


   Results Top


A total of 601 patients with at least three years of infertility were examined. The age of the referred wives ranged from 21-38 years, with a mean of 27.81 years (SD 5.276), while the age of the husbands ranged from 25-42 years, with a mean of 32.09 years (SD 5.665). There was no significant correlation between the age and pericentric inversion of Chromosome 9. Using the G-banded technique among the 601 patients, 15 (2.5%) individual was found to have inversion 9 (p11q12). Inversion 9 was observed for just 1(0.33%) female, while it was seen in 14 cases of males (4.69%).

Only one case had the break point of (p11q13) which has not considered in statistical analysis.

The incidence of inversion 9 in male patients was found significantly higher than that in female partners (P<0.05). The total average amount of inversion in both male and females in this study (2.5%) is not significantly higher than normal population [Table - 1], [Figure - 1].


   Discussion Top


A summary of reports for various abnormalities associated with pericentric inversion 9 (p11q13) and (p11q12) is shown in [Table - 2]. The finding of homozygosity for a pericentric inversion of Chromosome 9 is rare [5] and none of our cases was homozygote. We have observed 2.5% inversion 9 in cases with infertility which is similar to the earlier report by Sasiadek et al[13] in the cases of recurrent spontaneous abortions. However, our results cannot be compared to normal or general population because the rate of inv (9) is reported in a wide range from 1-3% by other investigators. [5],[6],[7],[8],[9]

The major observations in this study was the difference of the rate of inv (9)(p11q12) between the male and female patients as shown in [Table - 1] and [Figure - 1]. In contrast to some other studies on inversions of other chromosomes, [14],[15] there is considerable difference in frequency of inv (9) among two sexes (P<0.05).

These results of inv (9) may explain some idiopathic male infertility. In fact pairing in spermatogenesis constitutes the main problem in inversion heterozygosis. This phenomenon can be more effective in male partners because of their higher rate of meiotic division. An odd number of crossover events (during the pachytene stage of meiosis I) within the inversion segment can lead to two monocentric recombinants with reciprocal duplications/deficiencies in the sperms, ending up in a risk of inheriting such an imbalance when conception occurs. However, it has been shown that the classical assumption that loops are invariably present at meiotic prophase to realize a homologous pairing in inversion heterozygotes [16],[17],[18],[19],[20],[21] however, the other reports do not agree. [22] These results indicate that inv (9) may often cause clinical problems in offspring of the carriers and infertility with sex related unknown certain mechanism.


   Acknowledgment Top


This work was part of project No. 466-11, supported partly by Royan Institute[28].

 
   References Top

1.Hartl DL. Our uncertain heritage: Genetics and human diversity. 5 th ed. Harper and Row Publishers: New York; 2000. p. 181-8.  Back to cited text no. 1      
2.Gardner RJ, Sutherland G. Inversions. In: Chromosomal Abnormalities and Genetic Counseling, 3 rd ed. Oxford University Press: New York; 2004.  Back to cited text no. 2      
3.Mange AP, Mange EJ. Genetics: Human aspects. 4 th ed. Saunders College: Philadelphia; 1998. p. 170-2.  Back to cited text no. 3      
4.Abdous A, Pen-Ming L. Ming, Hosam T, Salem E, Reece A. The clinical importance of pericentric inversion of chromosome 9 in prenatal diagnosis. J Mat Fetal Investigation 1997;7:126-8.   Back to cited text no. 4      
5.Cotter PD, Babu A, McCurdy LD, Caggana M, Willner JP, Desnick RJ. Homozygosity for pericentric inversions of chromosome 9. Prenatal diagnosis of two cases. Ann Genet 1997;40:222-6.  Back to cited text no. 5      
6.Mokhtar MM. Chromosomal aberrations in children with suspected genetic disorders. EMHJ 1997;3:114-22.  Back to cited text no. 6      
7.Kim SS, Jung SC, Kim HJ, Moon HR, Lee JS. Chromosome abnormalities in a referred population for suspected chromosomal aberrations: A report of 4117 cases. J Korean Med Sci 1999;14:373-6.  Back to cited text no. 7      
8.Toyota T, Shimizu H, Yamada K, Yoshitsugu K, Meerabux J, Hattori E, et al. Karyotype analysis of 161 unrelated schizophrenics: No increased rates of X chromosome mosaicism or inv (9), using ethnical matched and age-stratified controls. Schizophr Res 2001;52:171-9.  Back to cited text no. 8      
9.Teo SH, Tan M, Knight L, Yeo SH, Ng I. Pericentric of inversion 9-incidence and clinical significance. Ann Acad Med Singapore 1995;24:302-4.  Back to cited text no. 9      
10.Cheong KF, Knight LA, Tan M, Ng IS. Variants of chromosome 9 inphenotypically normal individuals. Ann Acad Med Singapore 1997;26:312-4.  Back to cited text no. 10      
11.Verma RS, Babu A. Human chromosomes. Manual of Basic techniques, 2 nd ed. McGraw -Hill: New York; 1995.  Back to cited text no. 11      
12.ISCN. An International System for Human Cytogenetic Nomenclature. Mitelman F, editor. Karger: Basel; 1995.  Back to cited text no. 12      
13.Sasiadek M, Haus O, Lukasik-Majchrowska M, Slezak Paprocka-Borowicz M, Busza H, Plewa R, et al. Cytogenetic analysis in couples with spontaneous abortions. Ginekol Pol 1997;68:248-52.  Back to cited text no. 13      
14.Fraisse J, Philip T, Bertheas MF, Lauras B. Six cases of partial duplication-deficiency 21 syndrome: 21(dupq22delp23) due to maternal pericentric inversion: inv(21)(p12;q22). A family study. Ann Genet 1986;29:177-80.  Back to cited text no. 14      
15.Daniel A, Hook EB and Wulf G. Risks of unbalanced progeny at amniocentesis to carriers of chromosome rearrangements: Data from United States and Canadian laboratories. Am J Med Genet 1989;33:14-23.   Back to cited text no. 15      
16.Gabriel-Robez O, Ratomponirina C, Rumpler Y, Le Marec B, Luciani JM, Guichaoua MR. Synapsis and synaptic adjustment in an infertile human male heterozygous for a pericentric inversion in chromosome 1. Hum Genet 1986;72:148-52.   Back to cited text no. 16      
17.Gabriel-Robez O, Ratomponirina C, Croquette M, Maetz JL, Couturier J and Rumpler Y Reproductive failure and pericentric inversion in man. Andrologia 1987;19:662-9.  Back to cited text no. 17      
18.Guichaoua MR, Gabriel-Robez O, Ratomponirina C, Delafontaine D, Le Marec B, Taillemite JL, et al. Meiotic behaviour of familial pericentric inversions of chromosomes 1 and 9. Ann Genet 1986;29:207-14.  Back to cited text no. 18      
19.Saadallah N, Hulten M. EM investigations of surface spread synaptonemal complexes in a human male carrier of a pericentric inversion inv (13) (p12q14): The role of heterosynapsis for spermatocyte survival. Ann Hum Genet 1986;50:369-83.  Back to cited text no. 19      
20.Batanian J, Hulten MA. Electron microscopic investigations of synaptonemal complexes in an infertile human male carrier of a pericentric inversion inv(1)(p32q42). Regular loop formation but defective synapsis including a possible interchromosomal effect. Hum Genet 1987;76:81-9.  Back to cited text no. 20      
21.Malan V, Pipiras E, Sifer C, Kanafani S, Cedrin-Durnerin I, Martin-Pont B, et al. Chromosome segregation in an infertile man carrying a unique pericentric inversion, inv(21)(p12q22.3), analysed using fluorescence in situ hybridization on sperm nuclei: Significance for clinical genetics. A case report. Hum Reprod 2006;21:2052-6.  Back to cited text no. 21      
22.Chandley AC, McBeath S, Speed RM, Yorston L, Hargreave TB. Pericentric inversion in human chromosome 1 and the risk for male sterility. J Med Genet 1987;24:325-34.  Back to cited text no. 22      
23.Sasagawa I, Ishigooka M, Kubota Y, Tomaru M, Hashimoto T, Nakada T. Pericentric inversion of chromosome 9 in infertile men. Int Urol Nephrol 1998;30:203-7.  Back to cited text no. 23      
24.Pia Verri A, Cimbro C. Observation of an Asperger Syndrome's case with a diagnosis in adulthood and a pericentric inversion chromosome 9. Minerva Psichiatrica 2002;43:38.  Back to cited text no. 24      
25.Stanojevic M, Stipoljev F, Koprcina B, Kurjak A. Oculo-auriculo-vertebral (Goldenhar) spectrum associated with pericentric inversion 9: Coincidental findings or ethiologic factor? J Craniofac Genet Dev Biol 2000;20:150-4.  Back to cited text no. 25      
26.Baccetti B, Collodel G, Crisa D, Moretti E, Piomboni P. Ultrastructural sperm defects in two men, carriers of autosomal inversion. Andrologia 1997;29:277-82.  Back to cited text no. 26      
27.Miyaoka T, Seno H, Itoga M, Ishino H. A case of small cerebral cyst and pericentric inversion of chromosome 9 that developed schizophrenia-like psychosis. Psychiatry Clin Neurosci 1999;53:599-602.  Back to cited text no. 27      
28.Parmar RC, Sira P. Prenatal diagnosis of partial trisomy 21 associated with maternal balanced translocation 46, XX, der 21 t (21q;22q) with pericentric inversion of chromosome 9. J Postgrad Med 2003;49:154-6.  Back to cited text no. 28  [PUBMED]  Medknow Journal  


    Figures

  [Figure - 1]
 
 
    Tables

  [Table - 1], [Table - 2]


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