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PMID: 1415255 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis.

American journal of human genetics ·Vol. 51 ·No. 5 ·1992-11-00 ·Pages 1136-49

Gibbons RJ, Suthers GK, Wilkie AO, Buckle VJ, Higgs DR

Abstract

We have examined seven pedigrees that include individuals with a recently described X-linked form of severe mental retardation associated with alpha-thalassemia (ATR-X syndrome). Using hematologic and molecular approaches, we have shown that intellectually normal female carriers of this syndrome may be identified by the presence of rare cells containing HbH inclusions in their peripheral blood and by an extremely skewed pattern of X inactivation seen in cells from a variety of tissues. Linkage analysis has localized the ATR-X locus to an interval of approximately 11 cM between the loci DXS106 and DXYS1X (Xq12-q21.31), with a peak LOD score of 5.4 (recombination fraction of 0) at DXS72. These findings provide the basis for genetic counseling, assessment of carrier risk, and prenatal diagnosis of the ATR-X syndrome. Furthermore, they represent an important step in developing strategies to understand how the mutant ATR-X allele causes mental handicap, dysmorphism, and down-regulation of the alpha-globin genes.

MeSH Terms
Dosage Compensation, Genetic Female Genetic Carrier Screening Genetic Linkage Genetic Markers/genetics Globins/genetics Humans Intellectual Disability/genetics Lod Score Male Pedigree Risk Syndrome X Chromosome alpha-Thalassemia/genetics
Chemicals
Genetic Markers Globins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Gibbons R J
MRC Molecular Haematology Unit, John Radcliffe Hospital, Oxford, U.K.
Suthers G K
Wilkie A O
Buckle V J
Higgs D R
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
1992-11-00
Pages
1136-49
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1682840
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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