Mutations in intron 3 of GH‐1 gene associated with isolated GH deficiency type II in three Japanese families

Abstract

MutE has not been previously reported and is the fourth mutation associated with IGHD type II. The guanine residue mutated in mutA was the second nucleotide of a CpG dinucleotide, which is regarded as a hot spot for mutations by a methylation-deamination mechanism. Since mutA has previously been identified in three type II IGHD kindreds belonging to different ethnic backgrounds, this appears to be the most frequent GH-I gene mutation in IGHD with a dominant inheritance. Because de novo mutations appeared to have occurred in all three families analyzed in the present study and the presence or absence of these mutations can easily be tested by PCR and restriction enzyme digestion, not only the familial cases but also sporadic cases with IGHD should be examined for a possible mutation at the donor splice site of intron 3 in the GH-1 gene.