Parkinson D B, Shaw N J, Himsworth R L, Thakker R V
MRC Clinical Research Centre, Harrow, Middlesex, UK.
Hum Genet. 1993 Apr;91(3):281-4. doi: 10.1007/BF00218273.
We have identified a polymorphic tetranucleotide consisting of (AAAT)n within the first intron of the parathyroid hormone (PTH) gene, and have used this to investigate the segregation of the PTH gene and idiopathic hypoparathyroidism in 7 affected and 21 unaffected members from three families. An association between the PTH locus and autosomal dominant idiopathic hypoparathyroidism in one family was excluded by observing recombination between the two loci. In the remaining two families with autosomal recessive idiopathic hypoparathyroidism, the PTH locus was not similarly excluded. We had previously demonstrated a donor splice site mutation of the PTH gene in one of these families, and PTH gene abnormalities were therefore sought in the second of these families. DNA sequence analysis of the three exons, together with 4 exon-intron boundaries and the promoter region of the PTH gene revealed no abnormalities, thereby indicating molecular pathology at another locus. Thus, our analysis of idiopathic hypoparathyroidism reveals genetic heterogeneity for this disorder. In addition, our identification of a microsatellite polymorphism of the PTH gene should help further segregation studies of this locus in families with parathyroid disorders.
我们在甲状旁腺激素（PTH）基因的第一个内含子中鉴定出一个由（AAAT）n组成的多态性四核苷酸，并利用它来研究三个家族中7名患病成员和21名未患病成员中PTH基因的分离情况以及特发性甲状旁腺功能减退症。通过观察两个位点之间的重组，排除了一个家族中PTH基因座与常染色体显性特发性甲状旁腺功能减退症之间的关联。在其余两个患有常染色体隐性特发性甲状旁腺功能减退症的家族中，PTH基因座未被类似地排除。我们之前在其中一个家族中证实了PTH基因的一个供体剪接位点突变，因此在另一个家族中寻找PTH基因异常情况。对PTH基因的三个外显子、4个外显子-内含子边界以及启动子区域进行DNA序列分析，未发现异常，从而表明分子病理学存在于另一个基因座。因此，我们对特发性甲状旁腺功能减退症的分析揭示了该疾病的遗传异质性。此外，我们对PTH基因微卫星多态性的鉴定应有助于对甲状旁腺疾病家族中该基因座进行进一步的分离研究。
