Refinement of the genetic cause of ATR-16 |
| |
Authors: | Cornelis L Harteveld Marjolein Kriek Emilia K Bijlsma Zoran Erjavec Deepak Balak Marion Phylipsen Astrid Voskamp Emmanora di Capua Stefan J White Piero C Giordano |
| |
Institution: | (1) Department of Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center (LUMC), 2333RC Leiden, The Netherlands;(2) Delfzicht Ziekenhuis, Delfzijl, The Netherlands |
| |
Abstract: | Alpha thalassemia retardation associated with chromosome16 (ATR-16 syndrome) is defined as a contiguous gene syndrome resulting
from haploinsufficiency of the α-globin gene cluster and genes involved in mental retardation (MR). To date, only few cases
have been described which result from pure monosomy for a deletion of 16p. In most of these cases the deletion was identified
by densitometric analysis of Southern blot results or by Fluorescent In Situ Hybridization analysis, and these alterations
have not been mapped in detail. In this study, we have fine mapped deletions causing α-thalassemia within 2 Mb from the telomere
of 16p by multiplex ligation-dependent probe amplification (MLPA). We have developed a rapid and simple test for high resolution
mapping of rearrangements involving the tip of the short arm of chromosome 16 by incorporating 62 MLPA probes spaced approximately
10–200 kb over a region of 2 Mb from the telomere. One deletion of approximately 900 kb without MR was identified in addition
to three de novo deletions varying between 1.5 and 2 Mb causing ATR-16 in three patients having mild MR and α-thalassemia.
Two were found by chance to be ATR-16 because they were included in a study to search for telomeric loss in MR and not by
hematological analysis. This would plead for more alertness when a persistent microcytic hypochromic anemia at normal ferritin
levels is observed as suggestive for the ATR-16 syndrome. The region on chromosome 16p for which haploinsufficiency leads
to the dysmorphic features and MR typical for ATR-16, has been narrowed down to a 800 kb region localized between 0.9 and
1.7 Mb from the telomere. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|