No influence of parental origin of intact X chromosome and/or Y chromosome sequences on three-year height response to growth hormone therapy in Turner syndrome

Abstract

PurposeWhether parental origin of the intact X chromosome and/or the presence of Y chromosome sequences (Yseq) play a role in three-year height response to growth hormone (GH) were investigated.MethodsPaternal (Xp) or maternal (Xm) origin of X chromosome was assessed by microsatellite marker analysis and the presence of hidden Yseq was analyzed. The first-, second-, and third-year GH response was measured as a change in height z-score (Z_Ht) in Turner syndrome (TS) patients with 45,Xp (n=10), 45,Xm (n=15), and 45,X/46,X,+mar(Y) (Xm_Yseq) (n=8).ResultsThe mean baseline Z_Ht did not differ according to Xp or Xm origin, however the mean baseline Z_Ht was higher in the Xm_Yseq group than in Xm group, after adjusting for bone age delay and midparental Z_Ht (P=0.04). There was no difference in the height response to GH between the 3 groups. The height response to GH decreased progressively each year (P<0.001), such that the third-year increase in Z_Ht was not significant. This third-year decrease in treatment response was unaffected by Xp, Xm, and Xm_Yseq groups. Increasing GH dosage from the second to third-year of treatment positively correlated with the increase in Z_Ht (P=0.017).ConclusionThere was no evidence of X-linked imprinted genes and/or Yseq affecting height response to 3 years of GH therapy. Increasing GH dosages may help attenuate the decrease in third-year GH response in TS patients with 45,X and/or 46,X/+mar(Y).

Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting

“…Most of the studies analyzing parent-of-origin effects in TS, report a predominance of the maternal X, largely due to the non-viability of the karyotype 45,Y and a slight preferential loss of paternal sex chromosomes (66, 67,68,69,70,71). Several studies analyzed whether X-linked imprinting effects might be associated with distinct phenotypical features, with conflicting results (72,73,74).…”

The contribution of Xp22.31 gene dosage to Turner and Klinefelter syndromes and sex-biased phenotypes

“…A second possibility is the presence of cryptic Y-linked sequences in the cells of some individuals; the limited gene content of these sequences, their restricted expression pattern, and their comparative rarity (<10% of TS cases) indicates that their contribution to most TS phenotypes is limited (although there may be a possible association with increased gonadal cancer risk (Dabrowski et al, 2020;Kwon et al, 2017). The parental origin of the intact X chromosome in TS cases may also influence phenotype, although results from studies comparing physical and brain/behavioural phenotypes in subjects with maternally-or paternally-inherited intact X chromosomes are inconsistent and to date, no candidate genomically-imprinted X-linked genes have been identified in humans (Bondy et al, 2012;Davies, 2010;Hamelin et al, 2006;Ko et al, 2010;Lee et al, 2014;Lepage et al, 2013;O'Donoghue et al, 2020;Sagi et al, 2007;Skuse et al, 1997).…”