Human subtelomeric aberrations in the Hong Kong population

Intellectual disability (ID) is a common clinical problem, affecting approximately 2% of the population. The causes of ID can be either genetic, environmental, or a combination of both. Chromosomal abnormalities are a major cause of ID. They are more commonly seen in patients with moderate-severe ID than in patients with mild ID, accounting for up to 40-50% of these cases. Subtelomeric aberrations constitute an important subset of chromosomal disorders which have been increasingly recognised in recent years. The reported detection rate for subtelomeric aberrations in idiopathic moderate-severe ID is approximately 3.6%. The types of subtelomeric aberrations seen are similar to gross chromosomal abnormalities, in which isolated deletion is the most common, followed by deletion/duplication, and other complex rearrangements. 3000 unselected patients with ID or dysmorphism presenting to a clinical genetic service during the years 1986-2010 were screened, half by review of clinical records and photographs and half during the course of routine clinical review. Patients with clinical features suggestive of a subtelomeric syndrome were selected for review. This included repeated clinical examination, cytogenetic studies including FISH, and/or molecular MLPA investigations. Subsets of patients were further analysed by aCGH or MLPA multiprobe sets. A total of 600 patients were tested for subtelomeric aberrations, and 77 cases (12.8%) showed positive results. 31 patients (40%) had severe ID, 8 (10%) had moderate ID, 21 (27%) had mild ID, 10 (13%) had borderline intelligence, while 5 (7%) had normal intelligence, and 2 died in infancy. In 54 cases (70%), the aberrations were de novo, while 23 cases (30%) resulted from familial subtelomeric translocation. Thirteen families (17%) had a history of recurrent miscarriage (REC); however amongst the 23 cases with familial subtelomeric translocation, only 6 families (26%) had REC. Isolated terminal deletion (49 cases = 64%) was the most common type of subtelomeric aberration, followed by deletion/duplication (24 cases =31%), and isolated duplication (4 cases = 5%). MLPA 036/070 were found to be rapid screening tests for subtelomeric aberrations, and MLPA multiprobe sets and aCGH were useful for phenotype correlation. Vysis FISH analysis provided important information on telomere position. Facial features vary between ethnicities and this has major impact on dysmorphic features seen in Chinese patients. The features observed in Chinese patients with well-known subtelomeric syndromes are systematically described.

Grantor dc:publisher

UNSW, Sydney

Year dc:date

2013

Author dc:creator

• Lam, Albert Chuen-Fat

• Dysmorphology
• Subtelomeric aberrations
• Chromosomal abnormalities

Statement dc:rights

• open access
• CC BY-NC-ND 3.0
• free_to_read

Licence

• https://purl.org/coar/access_right/c_abf2
• https://creativecommons.org/licenses/by-nc-nd/3.0/au/

Language dc:language

EN

Identifier

https://doi.org/10.26190/unsworks/2500

OAI identifier oai:identifier

oai:unsworks.library.unsw.edu.au:1959.4/52978