This Article Full Text Full Text (PDF) All Versions of this Article: 92/3/846    most recent Author Manuscript (PDF) Submit a related Letter to the Editor View responses Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sagi, L. Articles by Hochberg, Z. Search for Related Content PubMed PubMed Citation Articles by Sagi, L. Articles by Hochberg, Z. Related Collections Female Endocrinology Pediatric Endocrinology

Clinical Significance of the Parental Origin of the X Chromosome in Turner Syndrome

Division of Endocrinology (L.S., N.Z.-L., O.B., Z.H.), Meyer Children’s Hospital, Haifa 31096, Israel; Department of Pediatric Endocrinology and Diabetes (A.G., E.M.-T.), Silesian University School of Medicine, 40287 Katowice, Poland; Pediatric Endocrinology (L.G., A.V.), Parma University, 143100 Parma, Italy; Department of Pediatrics (A.B.), Ismir University, 35360 Ismir, Turkey; Pediatric Endocrinology (Y.R., O.A.), Haemek Hospital, Afula 18101, Israel; Department of Pediatrics (T.B.), Asaf Harofeh Hospital, Tzrifin, Israel; Department of Biochemistry and Molecular Genetics (F.F.), Carmel Medical Center, Haifa, Israel; and Faculty of Medicine (F.F., Z.H.), Technion-Israel Institute of Technology, Haifa 31096, Israel

Address all correspondence and requests for reprints to: Ze’ev Hochberg, Meyer Children’s Hospital, Rambam Medical Center, P.O. Box 9602, Haifa 31096, Israel. E-mail: z_hochberg{at}rambam.health.gov.il.

Context: The phenotype in Turner syndrome (TS) is variable, even in patients with a supposedly nonmosaic karyotype. Previous work suggested that there were X-linked parent-of-origin effects on the phenotype.

Hypothesis: The TS phenotype is influenced by the parental origin of the missed X chromosome.

Design: This was a multicenter prospective study of TS patients and both their parents, determining parental origin of the X-chromosome, and characterizing the clinical phenotype.

Patients and Methods: Eighty-three TS patients and their parents were studied. Inclusion criteria were TS with karyotype 45,X or 46Xi(Xq). Four highly polymorphic microsatellite markers on the X-chromosome DMD49, DYSII, DXS1283, and the androgen receptor gene and three Y chromosome markers, SRY, DYZ1, and DYZ3.

Outcome Measures: The study determined the correlation between the parental origin of the X chromosome and the unique phenotypic traits of TS including congenital malformations, anthropometry and growth pattern, skeletal defects, endocrine traits, education, and vocation.

Results: Eighty-three percent of 45,X retained their maternal X (X^m), whereas 64% 46Xi(Xq) retained their paternal X (X^p, P < 0.001). Kidney malformations were exclusively found in X^m patients (P = 0.030). The X^m group had lower total and low-density lipoprotein cholesterol (P < 0.003), and higher body mass index SD score (P = 0.030) that was not maintained after GH treatment. Response to GH therapy was comparable. Ocular abnormalities were more common in the paternal X group (P = 0.017), who also had higher academic achievement.

Conclusions: The parental origin of the missing short arm of the X chromosome has an impact on overweight, kidney, eye, and lipids, which suggests a potential effect of an as-yet-undetermined X chromosome gene imprinting.

eLetters: