Autosomal-dominant isolated growth hormone deficiency (IGHD type II) with normal GH-1 gene.
BACKGROUND
Autosomal-dominant isolated GH deficiency (IGHD) is a rare disorder that is commonly believed to be due to heterozygous mutations in the GH-1 gene (GH-1). These mutations cause the production of a protein that affects the release of the product of the normal allele. Rarely, heterozygous mutations in the gene encoding for HESX-1 gene (HESX-1) may cause autosomal-dominant IGHD, with penetrance that has been shown to be variable in both humans and mice.


METHODS
We have sequenced the whole GH-1 in the index cases of 30 families with autosomal-dominant IGHD. In all the families other possible causes of GH deficiency and other pituitary hormones deficits were excluded. We here describe the clinical, biochemical and radiological picture of the families without GH-1 mutations. In these families, we also sequenced the HESX-1.


RESULTS
The index cases of the five families with autosomal-dominant IGHD had normal GH-1, including the intronic sequences. They had no HESX-1 mutations.


CONCLUSIONS
This study shows that GH-1 mutations are absent in 5/30 (16.6%) of the families with autosomal-dominant IGHD and raises the possibility that mutations in other gene(s) may be involved in IGHD with this mode of transmission.
Fintini
Danilo
D
Division of Endocrinology, Department of Medicine and Ilyssa Center for Molecular and Cellular Endocrinology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Salvatori
Roberto
R
Salemi
Souzan
S
Otten
Barto
B
Ubertini
Graziamaria
G
Cambiaso
Paola
P
Mullis
Primus E
PE
D000328:Adult; D000368:Aged; D002675:Child, Preschool; D004393:Dwarfism, Pituitary / Q000097:blood / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D010902:Pituitary Gland / Q000033:anatomy & histology; D017422:Sequence Analysis, DNA
D019382:Human Growth Hormone