Phenotype in X chromosome rearrangements: pitfalls of X inactivation study.
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.


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.


CONCLUSIONS
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.
Schluth
C
C
Laboratoire de Cytogénétique, Hôpital de Hautepierre, avenue Molière, 67098 Strasbourg cedex, France.
Cossée
M
M
Girard-Lemaire
F
F
Carelle
N
N
Dollfus
H
H
Jeandidier
E
E
Flori
E
E
D000015:Abnormalities, Multiple / Q000235:genetics; D000328:Adult; D001321:Autistic Disorder / Q000235:genetics; D002675:Child, Preschool; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X / Q000235:genetics*; D019175:DNA Methylation; D042522:DNA Replication Timing; D004392:Dwarfism / Q000235:genetics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D050172:Genes, X-Linked; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000196:embryology / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics; D010641:Phenotype; D011296:Prenatal Diagnosis; D011944:Receptors, Androgen / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics; D014424:Turner Syndrome / Q000235:genetics; D049951:X Chromosome Inactivation
D051860:Fragile X Messenger Ribonucleoprotein 1; D011944:Receptors, Androgen; C410798:AR protein, human; C497683:FMR1 protein, human