Pure subtelomeric microduplications as a cause of mental retardation

Abstract

Submicroscopic subtelomeric aberrations are a common cause of mental retardation (MR). New molecular techniques allow the identification of subtelomeric microduplications, but their frequency and significance are largely unknown. We determined the frequency of subtelomeric, pure microduplications in a cohort of 624 patients with MR and/or multiple congenital anomalies using multiplex ligation dependent probe amplification (MLPA) and delineated the identified microduplications using array based comparative genomic hybridization (array CGH). In 11 patients, MLPA revealed a subtelomeric duplication without a concurrent deletion. Additional fluorescence in situ hybridization studies and parental analyses showed that three had occurred de novo: one duplication 5q34qter (12.7 Mb), one duplication 9q34.13qter (7.2 Mb) and one duplication 9p24.2pter (4.1 Mb). Five microduplications (9p, 11q, 12q, 15q and 16p) appeared to be inherited from an unaffected parent, while in three cases (9p, 12p and 17p) the parents were not available for testing. Based on our findings and data from the literature, the three de novo duplications were the only ones likely to be disease-causing, leading to a frequency of pathogenic subtelomeric, pure microduplications of 0.5%. Our study shows that subtelomeric microduplications are an infrequent cause of MR and that additional clinical and family studies are required to assess their clinical significance.

Duplication 5q and Deletion 9p due to a t(5;9)(q34;p23) in 2 Cousins with Features of Hunter-McAlpine Syndrome and Hypothyroidism

“…The remaining instances were mostly intrachromosomal duplications and recombinants of pericentric inversions. The duplication size in our patients (17 Mb) compares with 5q34 ] q35 duplications in 11 previous cases, in particular those reported by Kariminejad et al [2009] and Ruiter et al [2007].…”

High frequency of submicroscopic chromosomal imbalances in patients with syndromic craniosynostosis detected by a combined approach of microsatellite segregation analysis, multiplex ligation-dependent probe amplification and array-based comparative genome hybridisation

“…It is of note that only one submicroscopic imbalance, a deletion 22q11.21, was found in a series of 63 patients with syndromic cleft defects,14 therefore, submicroscopic imbalances may not be common for all craniofacial abnormalities. Although subtelomeric duplications were suggested to be an infrequent cause of mental retardation (0.5%),15 13.9% of our patients had pure segmental duplications or trisomies, suggesting that increased gene dosage could be an important mechanism in craniosynostosis.…”

16p subtelomeric duplication: a clinically recognizable syndrome

“…Telomere analysis has also identified cryptic duplications of the subterminal region of chromosome 16p (dup16p), which was considered less rare than originally thought. 8,10,11 We report on two patients with dup16p recognized by fluorescent in situ hybridization (FISH) telomere analysis, presenting with closely overlapping facial features, neurological impairment, and urinary malformations. Susceptibility to vascular anomalies, in particular pulmonary hypertension and portal cavernoma, was found in one case.…”