Pericentric inversion of chromosome 9: Prevalence in 300 Down syndrome families and molecular studies of nondisjunction

Abstract

The incidence of Down syndrome (DS) families where one of the parents is an heterozygous carrier of pericentric inversion of the heterochromatic region of chromosome 9 -inv (9) (qh) -was determined in 3 independent groups of 100 families each. The total number of 17 such families found in the sample is significantly greater than the expected number of 5.73 for a sample of non-DS families of equal size. Consequently, the statistical association of the presence of inv (9) (qh) in one parent with the birth of a DS offspring, and the correlative 3-fold increased risk of a DS child for such families, seem to be demonstrated. A study of the origin of nondisjunction, using restriction fragment length polymorphism (RFLP) segregation analysis with a sufficient number of chromosome 21 specific probes, has provided complete information in 7 of 8 available families. Although the statistical interpretation of the results is not straightforward, due to the small size of the sample, the observed data do not contradict the assumption that the presence of inv (9) (qh) in a parent increases, by a factor of about 3, the chance that the offspring will inherit an extra chromosome 21 from that parent. Nevertheless, gathering further data appears desirable because stronger evidence would have relevance both for clinical implications and for the understanding of the function of heterochromatin, particularly with respect to meiotic and mitotic processes.

Research Article Down-Klinefelter syndrome (48,XXY,+21) in a neonate associated with congenital heart disease.

“…The pericentric inversion of chromosome 9 is a chromosomal heteromorphism and often found in humans (Hsu et al, 1987;Teo et al, 1995;Kim et al, 1999). According to Serra et al (1990), couples with one partner being the bearer of this chromosome 9 inversion have three times greater chances of conceiving a child with DS than couples without it.…”

Unusual segregation products in sperm from a pericentric inversion 17 heterozygote

“…Empirical studies have suggested the presence of an interchromosomal effect in chromosomal rearrangement carriers who produce children who are aneuploid for a chromosome not involved in the rearrangement (Canki and Dutrillaux 1979;Fryns and Van den Berghe 1980;Kaiser 1984;Serra et al 1990). However, these anecdotal reports could be the result of an ascertainment bias.…”

Behavioral and Developmental Characteristics of Children with Inversion of Chromosome 9 in Korea: A Preliminary Study

“…Gardner and Sutherland 3 insisted that inv(9) is a normal variant, based on the fact that its structure involves the reversal of a chromosome segment, including the centromere, in what is considered to be a balanced rearrangement, without any chromosome material being lost or gained at the microscopic level. However, the association of inv (9) with psychiatric disorders such as schizophrenia, 4-6 bipolar disorder, 7 mental retardation 8 and personality disorder 9 has been reported, and there have been several reports of its association with congenital urological anomalies such as undescended testes or hermaphroditism, and there have been many studies which reported recurrent spontaneous abortions or infertility in obstetric patients with inv (9), for whom there was no other apparent reason for such conditions. 2,10,11 In addition, a recent report posits the existence of various phenotypes of inv(9) depending on the differential breakpoint.…”

“…12 The incidence of inv (9) in the normal population has been found to differ from country to country. Serra et al 8 estimated the incidence to be 0.85% among newborn infants in European populations, while Hsu et al 13 reported that the incidence differed between ethnic groups, and was lowest in Asian populations (0.26%). However, Yamada, 11 Ko et al 14 and Teo 15 analyzed the data from several Asian countries, and reported the incidence of inv (9) in the Asian population to be 1.65%, 1.20% and 1.20%, respectively.…”

“…The incidences were lower in several countries, such as Taiwan and Singapore, but methodological differences might have influenced the results, as some of the studies involved were based on the analysis of newborns, while others were based on antenatal cytogenetic analysis. There have been reports of a higher prevalence of inv(9) in the Down syndrome population, 8 as well as in both the female and male members of habitual abortion couples with a history of more than two spontaneous first trimester abortions, 11 as compared to the normal population, but no specific phenotype has been proven to be associated with inv (9).…”