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背景家族性高醛固酮血症Ⅱ型(FH-Ⅱ)是单基因显性遗传的原发性醛固酮增多症,国外的家系连锁分析发现其致病基因可能位于7p22区域。目的对一个中国FH-Ⅱ家系进行连锁分析,确定其致病基因可能的位点。方法临床确定一个FH-Ⅱ家系,选取FH-Ⅱ候选基因区域(7p22)的微卫星标记(D7S531、D7S2521、D7S511、D7S481),进行PCR反应,通过对家系成员单倍型分析,确定可能的位点,并用多点参数分析方法计算其最大优势对数值(LOD值)。结果该家系中多人表现为高血压、低血钾、高醛固酮血症、低肾素血症、安体舒通试验阳性,且地塞米松治疗后醛固酮水平不下降,为明确的FH-Ⅱ家系。家系中3例明确受累成员及1例可疑受累成员存在同样的单倍型[D7S531(ac,n=24)-D7S2521(ac,n=11)-D7S511(ca,n=21)-D7S481(ac,n=16),n=微卫星短串联序列重复次数],但相同的单倍型也见于1例血压、血钾均正常的家系成员。外显率为1的情况下,各微卫星标记与该遗传家系表型间LOD值均<-4。结论该FH-Ⅱ家系未发现明确的与7p22区域间的连锁关系,但不除外延迟显性使得携带致病基因的患者延迟发病造成的影响。
Background Familial hyperformal aldosteronism type Ⅱ (FH-Ⅱ) is a single gene dominant inherited primary aldosteronism. A linkage analysis of pedigrees in foreign countries found that the gene may be located in the 7p22 region. Objective To carry out linkage analysis on a Chinese FH-Ⅱ pedigree to identify possible sites of its causative genes. Methods A FH-Ⅱ pedigree was identified clinically. Microsatellite markers (D7S531, D7S2521, D7S511 and D7S481) of FH-Ⅱ candidate gene region (7p22) were selected for PCR reaction. The possible haplotypes Point, and use the multi-point parameter analysis method to calculate the maximum dominant logarithm (LOD value). Results Many people in the pedigree showed high blood pressure, hypokalemia, hyperdiloneuria, hypoproteinemia, and spironolactone test, and the level of aldosterone did not decrease after treatment with dexamethasone. The results showed that FH-Ⅱ Family. The same haplotype [D7S531 (ac, n = 24) -D7S2521 (ac, n = 11) -D7S511 (ca, n = 21) -D7S481 (ac , n = 16), n = number of microsatellite short tandem repeats], but the same haplotype was also found in 1 pedigree with normal blood pressure and serum potassium. When the penetrance was 1, the LOD values of all the microsatellite markers and the phenotype of the genetic line were <-4. Conclusion The FH-Ⅱ pedigree did not find a clear linkage relationship with the 7p22 region, but no significant effect of delayed onset of disease was observed in patients with pathogenic genes.