Phenotype in X chromosome rearrangements: pitfalls of X inactivation study
- PMID: 16690229
- DOI: 10.1016/j.patbio.2006.04.003
Phenotype in X chromosome rearrangements: pitfalls of X inactivation study
Abstract
Objective: X inactivation pattern in X chromosome rearrangements usually favor the less unbalanced cells. It is correlated to a normal phenotype, small size or infertility. We studied the correlation between phenotype and X inactivation ratio in patients with X structural anomalies.
Patients and methods: During the 1999-2005 period, 12 X chromosome rearrangements, including three prenatal cases, were diagnosed in the Laboratoire de Cytogénétique of Strasbourg. In seven cases, X inactivation ratio could be assessed by late replication or methylation assay.
Results: In three of seven cases (del Xp, dup Xp, t(X;A)), X inactivation ratio and phenotype were consistent. The four other cases showed discrepancies between phenotype and X inactivation pattern: mental retardation and dysmorphism in a case of balanced X-autosome translocation, schizophrenia and autism in two cases of XX maleness and MLS syndrome (microphthalmia with linear skin defects) in a case of Xp(21.3-pter) deletion.
Conclusion: Discrepancies between X inactivation ratio and phenotype are not rare and can be due to gene disruption, position effect, complex microrearrangements, variable pattern of X inactivation in different tissues or fortuitous association. In this context, the prognostic value of X inactivation study in prenatal diagnosis will be discussed.
Similar articles
-
Mother and daughter with a terminal Xp deletion: implication of chromosomal mosaicism and X-inactivation in the high clinical variability of the microphthalmia with linear skin defects (MLS) syndrome.Eur J Med Genet. 2007 Nov-Dec;50(6):421-31. doi: 10.1016/j.ejmg.2007.07.004. Epub 2007 Aug 6. Eur J Med Genet. 2007. PMID: 17845869
-
Ring X and other structural X chromosome abnormalities: X inactivation and phenotype.Semin Reprod Med. 2001 Jun;19(2):147-57. doi: 10.1055/s-2001-15395. Semin Reprod Med. 2001. PMID: 11480912 Review.
-
Skewed X chromosome inactivation and breast and ovarian cancer status: evidence for X-linked modifiers of BRCA1.J Natl Cancer Inst. 2008 Nov 5;100(21):1519-29. doi: 10.1093/jnci/djn345. Epub 2008 Oct 28. J Natl Cancer Inst. 2008. PMID: 18957670
-
Prenatal diagnosis of de novo X;autosome translocations.Clin Genet. 2004 May;65(5):423-8. doi: 10.1111/j.0009-9163.2004.00255.x. Clin Genet. 2004. PMID: 15099352 Review.
-
Autism-associated familial microdeletion of Xp11.22.Clin Genet. 2008 Aug;74(2):134-44. doi: 10.1111/j.1399-0004.2008.01028.x. Epub 2008 May 21. Clin Genet. 2008. PMID: 18498374
Cited by
-
Familial cases of a submicroscopic Xp22.2 deletion: genotype-phenotype correlation in microphthalmia with linear skin defects syndrome.Mol Vis. 2013;19:311-8. Epub 2013 Feb 6. Mol Vis. 2013. PMID: 23401659 Free PMC article.
-
X chromosome inactivation in clinical practice.Hum Genet. 2009 Sep;126(3):363-73. doi: 10.1007/s00439-009-0670-5. Epub 2009 Apr 25. Hum Genet. 2009. PMID: 19396465 Review.
-
DNA methylation analysis of a de novo balanced X;13 translocation in a girl with abnormal phenotype: evidence for functional duplication of the whole short arm of the X chromosome.J Appl Genet. 2010;51(3):331-5. doi: 10.1007/BF03208863. J Appl Genet. 2010. PMID: 20720308
-
Human X chromosome inactivation and reactivation: implications for cell reprogramming and disease.Philos Trans R Soc Lond B Biol Sci. 2017 Nov 5;372(1733):20160358. doi: 10.1098/rstb.2016.0358. Philos Trans R Soc Lond B Biol Sci. 2017. PMID: 28947657 Free PMC article. Review.
-
Incorporation of 5-ethynyl-2'-deoxyuridine (EdU) as a novel strategy for identification of the skewed X inactivation pattern in balanced and unbalanced X-rearrangements.Hum Genet. 2016 Feb;135(2):185-92. doi: 10.1007/s00439-015-1622-x. Epub 2015 Dec 15. Hum Genet. 2016. PMID: 26670424
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
