X chromosome inactivation in carriers of Barth syndrome

被引:59
作者
Orstavik, KH
Orstavik, RE
Naumova, AK
D'Adamo, P
Gedeon, A
Bolhuis, PA
Barth, PG
Toniolo, D
机构
[1] Ulleval Univ Hosp, Dept Med Genet, N-0315 Oslo, Norway
[2] Temple Univ, Fels Inst Canc Res, Philadelphia, PA 19122 USA
[3] CNR, Ist Genet Biochim & Evoluzionist, I-27100 Pavia, Italy
[4] Womens & Childrens Hosp, Dept Cytogenet & Mol Genet, N Adelaide, SA, Australia
[5] Univ Amsterdam, Dept Neurol, Amsterdam, Netherlands
[6] Univ Amsterdam, Dept Pediat, Amsterdam, Netherlands
关键词
D O I
10.1086/302095
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Earth syndrome (BTHS) is a rare X-linked recessive disorder characterized by cardiac and skeletal myopathy, neutropenia, and short stature. A gene for BTHS, G4.5, was recently cloned and encodes several novel proteins, named "tafazzins." Unique mutations have been found. No correlation between the location or type of mutation and the phenotype of BTHS has been found. Female carriers of BTHS seem to be healthy, This could be due to a selection against cells that have the mutant allele on the active X chromosome. We therefore analyzed X chromosome inactivation in 16 obligate carriers of BTHS, from six families, using PCR in the androgen-receptor locus. An extremely skewed X-inactivation pattern (greater than or equal to 95:5), not found in 148 female controls, was found in six carriers. The skewed pattern in two carriers from one family was confirmed in DNA from cultured fibroblasts. Five carriers from two families had a skewed pattern (80:20-<95:5), a pattern that was found in only 11 of 148 female controls. Of the 11 carriers with a skewed pattern, the parental origin of the inactive X chromosome was maternal in all seven cases for which this could be determined. In two families, carriers with an extremely skewed pattern and carriers with a random pattern were found. The skewed X inactivation in 11 of 16 carriers is probably the result of a selection against cells with the mutated gene on the active X chromosome. Since BTHS also shows great clinical variation within families, additional factors are likely to influence the expression of the phenotype. Such factors may also influence the selection mechanism in carriers.
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页码:1457 / 1463
页数:7
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