Pearce S H, Wooding C, Davies M, Tollefsen S E, Whyte M P, Thakker R V
MRC Clinical Sciences Centre, Royal Postgraduate Medical School, London, UK.
Clin Endocrinol (Oxf). 1996 Dec;45(6):675-80. doi: 10.1046/j.1365-2265.1996.750891.x.
Pancreatitis is an unusual complication of the benign disorder familial hypocalciuric hypercalcaemia (FHH) such that it could represent a distinct subgroup of FHH. In order to study this, we investigated three FHH kindreds with recurrent pancreatitis for mutations of the extracellular calcium-sensing receptor (CaR) to identify a possible common genetic aetiology for typical FHH and that associated with pancreatitis.
Three FHH kindreds (18 affected, 14 unaffected members) in which the proband had presented with recurrent pancreatitis were identified. The entire 3234bp coding region of the CaR gene was examined by direct DNA sequencing using fluorochrome labelled dideoxy-terminators. Mutations were confirmed and demonstrated to co-segregate with FHH by restriction enzyme analysis.
Three novel heterozygous missense mutations (Asn178Asp, Arg220Gln and Pro221Ser) in the extracellular domain of the CaR were identified in each of the probands. These mutations, which co-segregated with the hypercalcaemia, were not detected as common polymorphisms in 55 unrelated normocalcaemic controls.
Familial hypocalciuric hypercalcaemia with recurrent pancreatitis is associated with calcium-sensing receptor mutations, and thus this variant has the same genetic aetiology as typical familial hypocalciuric hypercalcaemia.
胰腺炎是良性疾病家族性低钙血症性高钙血症（FHH）的一种罕见并发症，可能代表FHH的一个独特亚组。为了对此进行研究，我们调查了三个患有复发性胰腺炎的FHH家族，检测其细胞外钙敏感受体（CaR）的突变情况，以确定典型FHH以及与胰腺炎相关的FHH可能的共同遗传病因。
确定了三个FHH家族（18名患者，14名未患病成员），其中先证者患有复发性胰腺炎。使用荧光标记的双脱氧终止剂通过直接DNA测序检测CaR基因的整个3234bp编码区。通过限制性酶切分析确认突变并证明其与FHH共分离。
在每个先证者中均鉴定出CaR细胞外结构域的三个新的杂合错义突变（As n178Asp、Arg220Gln和Pro221Ser）。这些与高钙血症共分离的突变在55名无亲缘关系的血钙正常对照中未被检测为常见多态性。
伴有复发性胰腺炎的家族性低钙血症性高钙血症与钙敏感受体突变相关，因此这种变异型与典型家族性低钙血症性高钙血症具有相同的遗传病因。
