Molecular genetics of Turner syndrome: correlation with clinical phenotype and response to growth hormone therapy

Abstract

To correlate the origin of the retained X in Turner syndrome with phenotype, pre-treatment height and response to recombinant human growth hormone (rhGH) therapy, systematic clinical assessment and molecular studies were carried out in 33 Greek children with Turner syndrome and their parents including 18 children with 45,X and 15 with X-mosaicism. Microsatellite markers on X chromosomes (DXS101 and DXS337) revealed that the intact X was paternal (Xp) in 15/30 and maternal (Xm) in 15/30 children, while 3/33 families were non-informative. No significant relationship was found between parental origin of the retained X and birth weight/length/gestational age, blepharoptosis, pterygium colli, webbed neck, low hairline, abnormal ears, lymphoedema, short 4th metacarpal, shield chest, widely spaced nipples, cubitus valgus, pigmented naevi, streak gonads, and cardiovascular/renal anomalies. With regard to the children's pre-treatment height, there was a significant correlation with maternal height and target height in both Xm and Xp groups. No differences were found between Xm and Xp groups and the improvement of growth velocity (GV) during the first and second year of rhGH administration, while for both groups GV significantly improved with rhGH by the end of the first and the second year. To our knowledge, this is the first attempt to correlate the parental origin of Turner syndrome with the response to rhGH therapy.

Parental origin of normal X chromosomes in Turner syndrome patients with various karyotypes: Implications for the mechanism leading to generation of a 45,X karyotype

“…When largest data from various nations (United Kingdom, United States, Greece, Australia, Switzerland, Denmark, Spain, and Japan) are combined (to avoid multiple counting), 74.9% (227/303) of the X chromosomes in pure 45,X karyotypes are maternal in origin [Hassold et al, 1990;Lorda-Sanchez et al, 1992;Larsen et al, 1995;Martinez-Pasarell et al, 1998;Tsezou et al, 1999;Skuse et al, 1999;Uematsu et al, this report]. Although previous data of the parental origin for other karyotypes are limited, our results for patients with i(Xq) were also consistent with them.…”

“…The parental origin of the X chromosome of 45,X females has been the subject of many studies [Hassold et al, 1990[Hassold et al, , 1992Jacobs et al, 1990Jacobs et al, , 1997Cockwell et al, 1991;Loughlin et al, 1991;Mathur et al, 1991;Lorda-Sanchez et al, 1992;Chu et al, 1994;Collins et al, 1994;Larsen et al, 1995;Martinez-Pasarell et al, 1998;Skuse et al, 1999;Tsezou et al, 1999]. Most of these studies have shown that the majority (60-80%) of the X chromosomes are maternal in origin.…”

“…Most of these studies have shown that the majority (60-80%) of the X chromosomes are maternal in origin. However, studies on the parental origin of normal X chromosomes are relatively limited for TS females who have sex chromosome aberrations [Callen et al, 1987;Harbison et al, 1988;Lorda-Sanchez et al, 1991;Loughlin et al, 1991;Chu et al, 1994;Collins et al, 1994;Jacobs et al, 1997;James et al, 1997James et al, , 1998Tsezou et al, 1999].…”

A multicentre trial of recombinant growth hormone and low dose oestrogen in Turner syndrome: near final height analysis

“…Further work is required to define other characteristics of TS girls likely to benefit from GH therapy. Height gain with GH treatment is greater for shorter girls but is not demonstrably related to phenotypic features or to whether X chromosome microsatellite markers denote maternal or paternal origin 15. A heavier weight for height also correlates with GH treatment response 16…”

Turner's syndrome in dermatology

“…22 Attempts have been made to establish an association with parental origin of the X chromosome and high fetal loss and phenotypic manifestations in TS. 23,24 Thus far, 1 study demonstrates a strong correlation between retained maternal X chromosome, cardiovascular defects, and webbed neck deformity. 25 Imprinting has been similarly implicated in the inheritance of autoimmune diseases, with preferential paternal transmission.…”