Genomic imprinting in Turner syndrome: effects on response to growth hormone and on risk of sensorineural hearing loss.
BACKGROUND
Evidence exists for X-linked parent-of-origin effects in Turner syndrome, because phenotypic and cognitive profiles differ between 45,X(maternal) and 45,X(paternal) individuals.


OBJECTIVE
We evaluated the parent-of-origin effect of the intact X chromosome on spontaneous growth, GH-stimulated height gain, and frequency of sensorineural hearing loss in 54 subjects with Turner syndrome recruited from a Canadian randomized, controlled trial of GH supplementation to adult height.


RESULTS
Microsatellite analyses revealed that 72% of nonmosaic 45,X subjects retained an X(maternal), whereas 86% of nonmosaic 46,X,i(Xq) subjects carried an intact X(paternal). No significant differences were noted between X(maternal) and X(paternal) subjects for parents' heights, birth weight and length, and height, age, or bone age at study entry. In all subjects, and in those with X(maternal), baseline height sd score correlated with midparental height (all: r = 0.511, P < 0.001; X(maternal): r = 0.535, P = 0.001) and with mother's height (all: r = 0.510, P < 0.001; X(maternal): r = 0.574, P < 0.001) but only weakly with father's height (all: r = 0.334, P = 0.015; X(maternal): r = 0.292, P = 0.094). Using a linear model including age and height at GH initiation, subjects with X(maternal) had a greater mean height gain than those with X(paternal) (sd score difference and 95% confidence interval for all karyotypes was +0.43 and 0.04-0.82, P = 0.030, and for 45,X was +0.64 and 0.06-1.21, P = 0.031); X-linked imprinting explained 36-53% of the GH response. After pure tone audiometry testing, X(maternal) subjects were also less likely (P = 0.040) to have sensorineural hearing loss than X(paternal) subjects.


CONCLUSIONS
This study provides evidence of an X-linked imprinting effect on GH response and on sensorineural hearing loss in Turner syndrome and should fuel the search for candidate genes.
Hamelin
Catherine E
CE
Division of Experimental Medicine, McGill University, Montreal, Québec, Canada H3A 1A3.
Anglin
Greg
G
Quigley
Charmian A
CA
Deal
Cheri L
CL
D001827:Body Height / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting / Q000235:genetics*; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics*; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007621:Karyotyping; D018895:Microsatellite Repeats / Q000235:genetics; D010290:Parents; D011994:Recombinant Proteins / Q000627:therapeutic use; D014424:Turner Syndrome / Q000150:complications / Q000235:genetics*
D011994:Recombinant Proteins; D019382:Human Growth Hormone