MTDNA ANALYSIS SHOWS COMMON ANCESTRY IN 2 KINDREDS WITH X-LINKED RECESSIVE HYPOPARATHYROIDISM AND REVEALS A HETEROPLASMIC SILENT MUTATION

Two kindreds residing in eastern Missouri and exhibiting X-linked rece ssive idiopathic hypoparathyroidism have been described. Genealogical records extending back five generations revealed no common ancestor. T o investigate the possibility of relatedness, the DNA sequence of the mitochondrial D-loop was compared among several individuals in both ki ndreds. The mtDNA D-loop was amplified from the total DNA of individua ls by use of nested PCR reactions, and the resulting 430-bp fragment w as sequenced. The mtDNA sequence was identical among affected males an d their maternal lineage for individuals in both kindreds. Conversely, the mtDNA sequence of the fathers of the affected males differed from that of the maternal lineage at three to six positions. These results demonstrate that the two kindreds exhibiting X-linked recessive hypop arathyroidism are indeed related and that an identical gene defect is responsible for the disease. A further feature of the inheritance patt ern was examined when a unique point mutation was identified in the mt DNA of one branch of one of the kindreds. This mutation appears to be de novo and segregates in subsequent generations without obscuring rel atedness. In addition, the results of our study of mtDNA analysis indi cate that this approach may be of importance in investigating common a ncestry in other X-linked disorders.