Lack of mutations of preproparathyroid hormone gene in three kindreds with familial isolated hypoparathyroidism

The mutations of the preproparathyroid hormone (preproPTH) gene have been reported to cause some cases of familial isolated hypoparathyroidism (FIH). We investigated the preproPTH gene of five affected subjects of three Japanese kindreds with FIH. The mode of inheritance in FIH of two families was thought to be autosomal dominant, and the FIH of the other was probably inherited in an autosomal recessive manner. Exons 1, 2 and 3 of the preproPTH gene and its exon-intron boundaries were analyzed with either polymerase chain reaction and single strand conformational polymorphism, or direct sequencing of the amplified DNA. We did not detect any mutations in the amplified regions of the preproPTH gene, but an A to G transition in intron 1 was identified in all of the affected subjects. Among them, four were heterozygote, and the other was homozygote. This transition was considered to be a polymorphism, which was the same as reported previously. These results indicate that the preproPTH gene abnormalities are not responsible for FIH in these families. Further studies are required to elucidate whether genes coding for other molecules, such as calcium-sensing receptor, are involved in FIH.