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 7.6 kb deletion

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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 7.6 kb GH-1 deletion was identified in the patient, the brother and the father. Conclusion 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.