Subtelomeric rearrangements in Indian children with idiopathic intellectual disability/developmental delay: Frequency estimation & clinical correlation using fluorescence in situ hybridization (FISH)
Shruthi Mohan1, Teena Koshy1, Perumal Vekatachalam1, Sheela Nampoothiri2, Dhanya Yesodharan2, Kalpana Gowrishankar3, Jeevan Kumar3, Latha Ravichandran4, Santhosh Joseph5, Anupama Chandrasekaran5, Solomon F.D. Paul1
1 Department of Human Genetics, Sri Ramachandra University, Porur, India
2 Department of Paediatric Genetics, Amrita Institute of Medical Sciences, Kochi, India
3 Department of Medical Genetics, CHILDS Trust Medical Research Foundation, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, India
4 Department of Paediatrics, Sri Ramachandra University, Porur, India
5 Department of Radiology, Sri Ramachandra University, Porur, India
Solomon F.D. Paul
Department of Human Genetics, Sri Ramachandra University, Porur, Chennai 600 116, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background & objectives: Subtelomeres are prone to deleterious rearrangements owing to their proximity to unique sequences on the one end and telomeric repetitive sequences, which increase their tendency to recombine, on the other end. These subtelomeric rearrangements resulting in segmental aneusomy are reported to contribute to the aetiology of idiopathic intellectual disability/developmental delay (ID/DD). We undertook this study to estimate the frequency of subtelomeric rearrangements in children with ID/DD.
Methods: One hundred and twenty seven children with idiopathic ID/DD were tested for subtelomeric rearrangements using karyotyping and FISH. Blood samples were cultured, harvested, fixed and GTG-banded using the standard protocols.
Results: Rearrangements involving the subtelomeres were observed in 7.8 per cent of the tested samples. Detection of rearrangements visible at the resolution of the karyotype constituted 2.3 per cent, while those rearrangements detected only with FISH constituted 5.5 per cent. Five deletions and five unbalanced translocations were detected. Analysis of parental samples wherever possible was informative regarding the inheritance of the rearrangement.
Interpretation & conclusions: The frequency of subtelomeric rearrangements observed in this study was within the reported range of 0-35 per cent. All abnormal genotypes were clinically correlated. Further analysis with array technologies presents a future prospect. Our results suggest the need to test individuals with ID/DD for subtelomeric rearrangements using sensitive methods such as FISH.