Genetic heterogeneity of familial hyperkalaemic hypertension

被引:27
作者
Disse-Nicodeme, S
Desitter, I
Fiquet-Kempf, B
Houot, AM
Stern, N
Delahousse, M
Potier, J
Ader, JL
Jeunemaitre, X
机构
[1] Coll France, INSERM, U36, F-75005 Paris, France
[2] Assistance Publ Hop Paris, Hop Europeen Georges Pompidou, Dept Genet, Paris, France
[3] Hop Foch, Serv Nephrol, Suresnes, France
[4] Hop Cherbourg, Serv Nephrol, Toulouse, France
[5] Physiol Lab, Toulouse, France
关键词
hypertension; renal hyperkalaemia; Mendelian disorder; pseudohypoaldosteronism; genetic heterogeneity;
D O I
10.1097/00004872-200111000-00005
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Background Familial hyperkalaemic hypertension (FHH) is a Mendelian form of low-renin hypertension characterized by hyperkalaemia and hyperchloraemic acidosis despite a normal glomerular filtration rate. To date, three different loci have been identified, on chromosomes 1, 17 and 12. Objective To test for genetic linkage between the three FHH loci and three new affected kindreds. Design and methods Clinical, biological and genetic analyses were made of three kindreds, including 11 affected individuals among 25 members. Genotyping was performed using four series of microsatellite markers spanning the chromosomes 1, 17 and 12 loci, and the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene. Results Segregation of the trait in each kindred was compatible with an autosomal transmission, the affected individuals displaying reasonably consistent biochemical abnormalities and the expected variability in arterial hypertension. Multipoint linkage analysis excluded linkage with the four candidate loci in kindreds 1 and 2, but not with the chromosome 1 locus in kindred 3. Conclusion These results demonstrate further genetic heterogeneity and that a fourth gene is responsible for FHH in at least two unrelated kindreds. They suggest a variety of molecular defects leading to FHH. (C) 2001 Lippincott Williams & Wilkins.
引用
收藏
页码:1957 / 1964
页数:8
相关论文
共 28 条
[1]  
ADER JL, 1988, ARCH MAL COEUR VAISS, V81, P193
[2]   HYPERKALEMIA, HYPERTENSION AND SYSTEMIC ACIDOSIS WITHOUT RENAL FAILURE ASSOCIATED WITH A TUBLAR DEFECT IN POTASSIUM EXCRETION [J].
ARNOLD, JE ;
HEALY, JK .
AMERICAN JOURNAL OF MEDICINE, 1969, 47 (03) :461-+
[3]   FAMILIAL HYPERKALEMIA, HYPERTENSION, AND HYPORENINEMIA WITH NORMAL ALDOSTERONE LEVELS - TUBULAR DEFECT IN POTASSIUM HANDLING [J].
BRAUTBAR, N ;
LEVI, J ;
ROSLER, A ;
LEITESDORF, E ;
DJALDETI, M ;
EPSTEIN, M ;
KLEEMAN, CR .
ARCHIVES OF INTERNAL MEDICINE, 1978, 138 (04) :607-610
[4]   A new locus on chromosome 12p13.3 for pseudohypoaldosteronism type II, autosomal dominant form of hypertension [J].
Disse-Nicodème, S ;
Achard, JM ;
Desitter, I ;
Houot, AM ;
Fournier, A ;
Corvol, P ;
Jeunemaitre, X .
AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (02) :302-310
[5]  
DISSENICODEME S, 2001, IN PRESS ADV NEPHROL, V31
[6]   Furosemide and dDAVP for the treatment of pseudohypoaldosteronism type II [J].
Erdogan, G ;
Corapçioglu, D ;
Erdogan, MF ;
Hallioglu, J ;
Uysal, AR .
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 1997, 20 (11) :681-684
[7]   FAMILIAL HYPER-POTASSEMIA AND HYPERTENSION ACCOMPANIED BY NORMAL PLASMA ALDOSTERONE LEVELS - POSSIBLE HEREDITARY CELL-MEMBRANE DEFECT [J].
FARFEL, Z ;
IAINA, A ;
ROSENTHAL, T ;
WAKS, U ;
SHIBOLET, S ;
GAFNI, J .
ARCHIVES OF INTERNAL MEDICINE, 1978, 138 (12) :1828-1832
[8]  
GORDON RD, 1970, AUSTRALAS ANN MED, V19, P287
[9]   A NEW AUSTRALIAN KINDRED WITH THE SYNDROME OF HYPERTENSION AND HYPERKALEMIA HAS DYSREGULATION OF ATRIAL NATRIURETIC FACTOR [J].
GORDON, RD ;
RAVENSCROFT, PJ ;
KLEMM, SA ;
TUNNY, TJ ;
HAMLET, SM .
JOURNAL OF HYPERTENSION, 1988, 6 :S323-S326
[10]   HETEROGENEOUS HYPERTENSION [J].
GORDON, RD .
NATURE GENETICS, 1995, 11 (01) :6-9