MAPPING THE GENE CAUSING X-LINKED RECESSIVE IDIOPATHIC HYPOPARATHYROIDISM TO XQ26-XQ27 BY LINKAGE STUDIES

被引:51
作者
THAKKER, RV
DAVIES, KE
WHYTE, MP
WOODING, C
ORIORDAN, JLH
机构
[1] SHRINERS HOSP CRIPPLED CHILDREN,METAB RES UNIT,ST LOUIS,MO 63110
[2] MIDDLESEX HOSP,DEPT MED,LONDON W1N 8AA,ENGLAND
[3] JOHN RADCLIFFE HOSP,NUFFIELD DEPT CLIN MED,OXFORD OX3 9DU,ENGLAND
[4] WASHINGTON UNIV,MED CTR,DEPT MED,ST LOUIS,MO 63110
[5] WASHINGTON UNIV,MED CTR,DEPT PEDIAT,ST LOUIS,MO 63110
关键词
DNA linkage studies; X-linked hypoparathyroidism;
D O I
10.1172/JCI114712
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Idiopathic hypoparathyroidism has been reported to occur as an X-linked recessive disorder in two multigeneration kindreds. Affected individuals, who are males, suffer from infantile onset of epilepsy and hypocalcemia, which appears to be due to an isolated congenital defect of parathyroid gland development; females are not affected and are normocalcemic. We have performed linkage studies in these two kindreds (5 affected males, 11 obligate carrier females, and 44 unaffected members) and have used cloned human X chromosome sequences identifying restriction fragment length polymorphisms to localize the mutant gene causing this disorder. Our studies established linkage between the X-linked recessive idiopathic hypoparathyroid gene (HPT) and the DXS98 (4D.8) locus, peak LOD score = 3.82 (θ = 0.05), thereby mapping HPT to the distal long arm of the X chromosome (Xq26-Xq27). Multilocus analysis indicated that HPT is proximal to the DXS98 (4D.8) locus but distal to the F9 (Factor IX) locus, thereby revealing bridging markers for the disease. The results of this study will improve genetic counseling of affected families, and further characterization of this gene locus will open the way for elucidating the factors controlling the development and activity of the parathyroid glands.
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页码:40 / 45
页数:6
相关论文
共 32 条
[1]   FAMILIAL ISOLATED HYPOPARATHYROIDISM - A MOLECULAR GENETIC-ANALYSIS OF 8 FAMILIES WITH 23 AFFECTED PERSONS [J].
AHN, TG ;
ANTONARAKIS, SE ;
KRONENBERG, HM ;
IGARASHI, T ;
LEVINE, MA .
MEDICINE, 1986, 65 (02) :73-81
[2]  
ARNOLD A, 1989, J BONE MINER RES S, V4, pS378
[3]  
BARR DGD, 1971, HELV PAEDIATR ACTA, V26, P507
[4]   2 ANONYMOUS X-SPECIFIC HUMAN SEQUENCES DETECTING RESTRICTION FRAGMENT LENGTH POLYMORPHISMS IN REGION XQ26-]QTER [J].
BOGGS, BA ;
NUSSBAUM, RL .
SOMATIC CELL AND MOLECULAR GENETICS, 1984, 10 (06) :607-613
[5]   FAMILIAL IDIOPATHIC HYPOPARATHYROIDISM [J].
BRONSKY, D ;
KIAMKO, RT ;
WALDSTEIN, SS .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1968, 28 (01) :61-+
[6]  
BROWN WT, 1987, CYTOGENET CELL GENET, V46, P587
[7]   INSITU HYBRIDIZATION AND TRANSLOCATION BREAKPOINT MAPPING .3. DIGEORGE SYNDROME WITH PARTIAL MONOSOMY OF CHROMOSOME-22 [J].
CANNIZZARO, LA ;
EMANUEL, BS .
CYTOGENETICS AND CELL GENETICS, 1985, 39 (03) :179-183
[8]  
CARPENTER NJ, 1987, CYTOGENET CELL GENET, V46, P590
[9]  
CONNOR JM, 1987, CYTOGENET CELL GENET, V46, P598
[10]   REPORT OF THE COMMITTEE ON THE GENETIC CONSTITUTION OF THE X-CHROMOSOMES AND Y-CHROMOSOMES [J].
DAVIES, KE ;
MANDEL, JL ;
WEISSENBACH, J ;
FELLOUS, M .
CYTOGENETICS AND CELL GENETICS, 1987, 46 (1-4) :277-315