A body of evidence shows that children born out of consanguineous marriages suffer from several congenital disorders. This is particularly so in the case of children born out of union involving first cousins. The problem in close relative marriages surfaces when a person carries a defect in any of the genes associated with some form of disease and marries a person from the same kindred who also shares the defect. The child inherits two copies of this faulty gene, and thus has the disease.
Now, a study published recently in the journal Cytogenetic and Genome Research reports the presence of a ring chromosome in a two-year-old child of a first-cousin marriage. The child died when he was seven years old.
Ring chromosomes are rare unbalanced chromosomal abnormalities that occur in about 1 in 50,000 foetuses, says the paper. Ring chromosomes occur when the tips of the chromosome are broken at both ends followed by fusion of these ends or telomere-telomere fusion of the chromosome without the loss of genetic material.
“In this case, the telomere was intact but the telomeric repeats may have got lost during the formation of the ring chromosome,” says Dr. Lakshmi R. Kandukuri from the Centre for Cellular and Molecular Biology, Hyderabad. One of the chromosomes of the chromosome 9 pair exhibited the ring structure.
As a result of the ring chromosome 9, the child had developmental delay. “The two-year milestones were not reached on time but were delayed,” she says. The child also had facial dysmorphic features including low-set ears and upward slanting eyes, microcephaly, suffered from seizures and had mild spasticity.
Karyotyping revealed that different chromosomal abnormalities were present in differing proportions. The anomalies comprised of a ring chromosome 9, two ring chromosomes, a large ring chromosome 9 with two centromeres and finally absence of the ring chromosome itself.
Detailed study of the ring chromosome 9 revealed gene loss due to deletion of a particular segment of the chromosome. However, the loss was seen in only one arm of the abnormal chromosome. Chromosomal microarray analysis revealed a 15.7 Mb deletion in one arm of the chromosome 9. “This region is crucial as it carries genes associated with seizure disorder, speech impairment and intellectual disability,” says Dr. Kandukuri.
Though the observable characteristics of the child could be attributed to the loss of genes encompassed in this region, in-depth studies including molecular characterization of the genes involved are required to elucidate the contributory mechanism and to thus correlate the different features such as developmental delay, facial characteristics, seizure and microcephaly to the genotype, she stressed.