A case with isolated growth hormone deficiency caused by compound heterozygous mutations in GH-1: a novel missense mutation in the initiation codon and a 7.6kb deletion.
OBJECTIVE
To characterize the cause of a sporadic isolated growth hormone deficiency in a single patient.


METHODS
Genomic DNA was extracted from blood samples of the patient and his family. Exons and exon-intron junctions of the GH-1 gene were amplified by PCR and sequenced. To characterize possible GH-1 deletions we performed Southern blot analysis and PCR-restriction fragment length analyses.


RESULTS
An adenine to guanine mutation at the first nucleotide of the initiation codon (Met [ATG](-26)Val [GTG]) of the GH-1 gene was identified in the patient and the mother. A 7.6kb GH-1 deletion was identified in the patient, the brother and the father.


CONCLUSIONS
The patient was a compound heterozygote for an allele bearing a Met(-26)Val missense mutation inherited from his mother and an allele containing deletion of the entire GH-1 gene inherited from his father. The present missense mutation has not been described previously. Attention should be paid to the heterozygous gene deletion that is difficult to detect by PCR-based genetic analysis. The patient responded to GH replacement therapy fairly well, without developing anti-hGH antibody.
Hayashi
Yoshitaka
Y
Department of Genetics, Division of Stress Adaptation and Protection, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. hayashiy@riem.nagoya-u.ac.jp
Kamijo
Takashi
T
Yamamoto
Michiyo
M
Murata
Yoshiharu
Y
Phillips
John A
JA
Ogawa
Masamichi
M
Seo
Hisao
H
D000483:Alleles; D018387:Codon, Initiator / Q000235:genetics; D004393:Dwarfism, Pituitary / Q000235:genetics*; D006579:Heterozygote; D019382:Human Growth Hormone / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008715:Methionine / Q000737:chemistry / Q000235:genetics; D020125:Mutation, Missense; D010375:Pedigree; D017422:Sequence Analysis, DNA; D014633:Valine / Q000737:chemistry / Q000235:genetics
D018387:Codon, Initiator; D019382:Human Growth Hormone; D008715:Methionine; D014633:Valine