Congenital sodium diarrhea is an autosomal recessive disorder of sodium/proton exchange but unrelated to known candidate genes.
Congenital sodium diarrhea is an autosomal recessive disorder of sodium/proton exchange but unrelated to known candidate genes.
复制标题
先天性钠腹泻是一种钠/质子交换的常染色体隐性遗传疾病，但与已知的候选基因无关。
作者：
Thomas Müller;C. Wijmenga;Alan D. Phillips;A. Janecke;Roderick J Houwen;Helmut Fischer;H. Ellemunter;M. Frühwirth;Felix Offner;Sabine Hofer;Wilfried Müller;Ian W. Booth;P. Heinz
背景与目标
先天性钠腹泻 (CSD) 是由钠/质子交换缺陷引起的，仅报告了 6 例散发病例。该疾病的遗传学尚未确定。我们研究了在奥地利一个有限的农村地区发现的 5 名患有分泌性腹泻的婴儿，以确定传播模式以及已知编码钠/质子交换器 (NHE) 的候选基因的参与情况。
方法
我们收集了 5 名受影响患者的临床和实验室数据，分析了他们的家族谱系，并在已知含有 NHE 基因的 4 个候选区域中进行了纯合性作图和多点连锁分析研究。
结果
5 名患者中有 4 名的 CSD 诊断依据为每日粪便钠排泄量在 98 至 190 mmol/L 之间、低钠血症、代谢性酸中毒以及尿钠浓度低至正常。对受影响的 2 个 CSD 家庭的系谱分析显示，父母有近亲血缘关系，并且 5 代以前有一个共同的单一祖先。纯合性作图和/或多点连锁分析排除了1号染色体上的NHE1基因座、2号染色体上的NHE2基因座、5号染色体上的NHE3基因座和16号染色体上的NHE5基因座作为该家系中CSD的潜在候选基因。 NHE4 的结果尚无定论，因为目前尚不清楚该 NHE 基因在人类染色体中的精确位置。
结论
我们的数据表明，CSD 是一种常染色体隐性遗传疾病，但与编码目前已知的钠/质子交换体的 NHE1、NHE2、NHE3 和 NHE5 基因的突变无关。
BACKGROUND & AIMS
Congenital sodium diarrhea (CSD) is caused by defective sodium/proton exchange with only 6 sporadic cases reported. The genetics of the disease have not been established. We studied 5 infants with secretory diarrhea, identified in a circumscribed rural area in Austria, to define the mode of transmission and the involvement of candidate genes known to encode for sodium/proton exchangers (NHEs).
METHODS
We collected clinical and laboratory data from 5 affected patients, analyzed the pedigrees of their families, and performed homozygosity mapping and multipoint linkage analysis studies in 4 candidate regions known to contain NHE genes.
RESULTS
The diagnosis of CSD in 4 of 5 patients was based on daily fecal sodium excretion between 98 and 190 mmol/L, hyponatremia, metabolic acidosis, and low-to-normal urinary sodium concentrations. Pedigree analysis of the affected 2 CSD families revealed parental consanguinity and a common single ancestor 5 generations ago. Homozygosity mapping and/or multipoint linkage analysis excluded the NHE1 locus on chromosome 1, NHE2 locus on chromosome 2, NHE3 locus on chromosome 5, and NHE5 locus on chromosome 16 as potential candidate genes for CSD in this pedigree. Results on NHE4 were inconclusive because the precise chromosomal location of this NHE gene in humans is currently unknown.
CONCLUSIONS
Our data indicate that CSD is an autosomal recessive disorder but is not related to mutations in the NHE1, NHE2, NHE3, and NHE5 genes encoding for currently known sodium/proton exchangers.
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DOI：
10.1152/ajpgi.1996.271.3.g483
发表时间：
1996-09-01
影响因子：
4.5
作者：
Dudeja, PK;Rao, DD;Ramaswamy, K
通讯作者：
Ramaswamy, K
人类 Na /H 交换基因：通过辐射杂交作图鉴定多态性和终末期肾病连锁分析。
DOI：
10.1161/01.hyp.35.1.135
发表时间：
2000
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Yu,H;Freedman,BI;Rich,SS;Bowden,DW
通讯作者：
Bowden,DW
影响因子：
4.4
作者：
BRANT, SR;BERNSTEIN, M;JABS, EW
通讯作者：
JABS, EW
健康和疾病过程中 Na /H 交换剂的生理和分子方面。
DOI：
--
发表时间：
1995
期刊：
Journal of investigative medicine : the official publication of the American Federation for Clinical Research
影响因子：
--
作者：
Soleimani,M;Singh,G
通讯作者：
Singh,G