Clinical significance of the parental origin of the X chromosome in turner syndrome.
BACKGROUND
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.


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


METHODS
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.


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.


METHODS
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.
Sagi
Liora
L
Division of Endocrinology, Meyer Children's Hospital, Rambam Medical Center, P.O. Box 9602, Haifa 31096, Israel.
Zuckerman-Levin
Nehama
N
Gawlik
Aneta
A
Ghizzoni
Lucia
L
Buyukgebiz
Atilla
A
Rakover
Yardena
Y
Bistritzer
Tzvi
T
Admoni
Osnat
O
Vottero
Alessandra
A
Baruch
Oshrat
O
Fares
Fuad
F
Malecka-Tendera
Ewa
E
Hochberg
Ze'ev
Z
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology; D013006:Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D040582:Inheritance Patterns; D010290:Parents; D012923:Social Class; D014424:Turner Syndrome / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology
D013006:Growth Hormone