Ann Pediatr Endocrinol Metab.  2014 Sep;19(3):127-134. 10.6065/apem.2014.19.3.127.

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

• Lee HJ
• Jung HW
• Lee GM
• Kim HY
• Kim JH
• Lee SH
• Kim JH
• Lee YA
• Shin CH
• Yang SW

• KMID: 2134079
• DOI: http://doi.org/10.6065/apem.2014.19.3.127

Abstract

PURPOSE
Whether 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.
METHODS
Paternal (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).
RESULTS
The 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).
CONCLUSION
There 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).

Keyword

Turner syndrome; Growth hormone; X chromosome; Y chromosome; Genomic imprinting

MeSH Terms

Genomic Imprinting
Growth Hormone*
Humans
Microsatellite Repeats
Parents*
Turner Syndrome*
X Chromosome*
Y Chromosome*
Growth Hormone

Figure

• 

  Fig. 1 While no difference in baseline Z_Ht_Lyon between Xp and Xm groups was observed, the Xm_Yseq group had a higher baseline Z_Ht_Lyon than the Xm group, after adjusting for BA delay and Z_MPH (P=0.04). Z_Ht_Lyon, height z-score according to Turner syndrome specific height reference by Lyon et al.12); Xp, paternally derived X chromosome; Xm, maternally derived X chromosome; Xm_Yseq, 45,X/46,X,+mar(Y); BA delay, difference between chrolonological age and BA; Z_MPH, midparental height z-score.

• 

  Fig. 2 (A) Z_Ht_Lyon significantly increased during 3 years of GH treatment (P<0.001). There was no difference between the three groups (Xp, Xm, Xm_Yseq) as to the overall pattern of change in Z_Ht_Lyon with GH treatment. The differences in mean Z_Ht_Lyon between the 3 groups were no longer significant, after adjusting for baseline Z_Ht_Lyon, CA at the start of GH, BA delay, GH dose and Z_MPH. (B) The percentage of poor responders (△Z_Ht_Lyon<0.1) increased progressively from the first, second, and third years of treatment by 9.1%, 27.3%, and 51.5% respectively. (C) The percentage of short patients (Z_Ht_07Kor<-1.88) declined successively from 69.7% at the time of GH commencement to 54.6% and 48.4% during the first and second years, but increased to 76.7% during the third year of treatment. GH, growth hormone; Z_Ht_Lyon, height z-score according to Turner syndrome specific height reference by Lyon et al.12); Xp, paternally derived X chromosome; Xm, maternally derived X chromosome; Xm_Yseq, 45,X/46,X,+mar(Y); CA, chronological age; BA delay, difference between CA and BA; and Z_MPH, midparental height z-score; △Z_Ht_Lyon, change in Z_Ht_Lyon; Z_Ht_07Kor, height z-score according to the 2007 Korean reference height values.

• 

  Fig. 3 The change in GH dose between second and third years of treatment showed a positive correlation with the third year height response (third-year △Z_Ht_Lyon), after adjusting for second-year △Z_Ht_Lyon (P=0.017). △Z_Ht_Lyon, change in height z-score according to Turner syndrome specific height reference by Lyon et al.12).

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