Growth hormone (GH-1) gene deletions in children with isolated growth hormone deficiency (IGHD).
OBJECTIVE
To detect growth hormone GH-1 gene deletions (6.7 kb, 7.6 kb, 7 kb) in familial/nonfamilial isolated growth hormone deficiency (IGHD) and note their clinical and investigative profile.


METHODS
Thirty (M16,F14) prepubertal IGHD patients aged 0.25 to 14 y, from 25 families were screened. Duration of growth failure, relevant history, clinical phenotype, and height SDS were recorded. Peak GH response to Clonidine (0.15 mg/m(2)), IGF-1, IGFBP-3 and pituitary/target gland hormones were studied. Genomic DNA of patients and family was analysed by PCR and DNA fragments were visualized on agarose gel electrophoresis.


RESULTS
This series was divided into deletion +ve, Group I (n=12,40%) inclusive of six familial/six nonfamilial patients, and deletion -ve Group II (n=18,60%), 5 familial/13 nonfamilial cases; in total 11/30 were familial. Onset of growth failure was earlier in Group I (p<0.001) mean 1.1 vs 4.7 y. Mean height SDS was -7 vs. -4.5 in Groups I/II (p<0.01), age at presentation 5.1 vs 8.6 y. Overhanging forehead, prominent eyes, hypoplastic facies characterized Group I with FBS <50 mg/dl in 50% and very low peak GH <0.04 vs 2.04 ng/ml (p<0.001) in Group II. In both groups IGF-1 and IGFBP3 were low, other hormones were normal and MRI showed hypoplastic adenohypophysis. 40% had GH-1 gene deletion (6.7 kb deletion in 83%, 7.6 kb and a compound heterozygote in 8% each).


CONCLUSIONS
In this series of 30 IGHD patients, frequency of GH-1 gene deletions (12/30) was 40%, and 54% among familial patients, and 31% with height SDS>-4. 83% had 6.7 kb deletion. Height SDS>-4, clinical phenotype, peak GH<1 ng/ml and hypoglycemia characterised IGHD Type IA.
Department of Pediatrics, Sir H.N. Hospital and Research Centre, Raja Rammohan Roy Road, Mumbai, India. drmeenadesai@gmail.com
Meena P
MP
Desai
Shilpa M
SM
Mithbawkar
Pradnya S
PS
Upadhye
Kavita K
KK
Shalia
D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004393:Dwarfism, Pituitary / Q000175:diagnosis / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005260:Female; D019382:Human Growth Hormone / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012189:Retrospective Studies; D017384:Sequence Deletion
D019382:Human Growth Hormone