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

• Published in: The journal of clinical endocrinology and metabolism 2007-03, Vol.92 (3), p.846-852
• Main Authors: Sagi, Liora, Zuckerman-Levin, Nehama, Gawlik, Aneta, Ghizzoni, Lucia, Buyukgebiz, Atilla, Rakover, Yardena, Bistritzer, Tzvi, Admoni, Osnat, Vottero, Alessandra, Baruch, Oshrat, Fares, Fuad, Malecka-Tendera, Ewa, Hochberg, Ze’ev
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Child; Child, Preschool; Chromosomes, Human, X; Endocrinopathies; Female; Fractures, Bone - epidemiology; Fundamental and applied biological sciences. Psychology; Growth Hormone - therapeutic use; Humans; Infant; Inheritance Patterns; Medical sciences; Parents; Social Class; Turner Syndrome - drug therapy; Turner Syndrome - epidemiology; Turner Syndrome - genetics; Turner Syndrome - psychology; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-0158

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 (Xm), whereas 64% 46Xi(Xq) retained their paternal X (Xp, P < 0.001). Kidney malformations were exclusively found in Xm patients (P = 0.030). The Xm 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.