1999 European Regional Conference Proceeding
May 12 - 16, 1999
| Conference: | 1999 European Regional Conference |
|---|---|
| Title: | Bartter syndrome with sensorineural deafness: molecular genetics |
| Author: | Ruf, Rainer |
| Institution: | Universitats Kinderklinik |
Bartter syndrome, an autosomal recessive salt-wasting tubulopathy, is characterized by severe polyuria in the neonate. It can be distinguished from NDI by the presence of hypokalemia with metabolic alkalosis, hypercalciuria, hyperreninsm, hyperaldosteronism and increased urinary prostaglandine E2 excretion. Three causative genes have been identified so far as a cause for Bartter syndrome (BS): For the antenatal subtype defects in the Na-K-2Cl (NKCC2) cotransporter (BS type 1)[1,2] and the potassium channel ROMK (BS type 2;)[3,4] were demonstrated. In the gene for the basolateral chloride channel CLC-Kb (CLCNKN) mutations were found in the antenatal as well as in the classical subtype (BS type 3;).[5] Recently, a gene locus for neonatal Bartter syndrome with sensorineural deafness (SND) was mapped to chromosome 1p31 in a Bedouin family.[6] Here we report linkage analysis at this locus for 6 Bartter families with SND using six neighbouring polymorphic microsatellite markers. In all families haplotype analysis was compatible with linkage of these markers and the disease locus. Recombinant events in two families defined an interval of 4 cM between flanking markers D1S2661 and D1S475. A physical YAC/PAC map was constructed with published STS markers and novel PAC end-sequence markers were generated. In order to obtain a complete transcriptional map with possible candidate genes, EST and cDNA markers were placed into the YAC/PACcontig. Identification of a gene for BS4 will offer new insight into the pathophysiology of renal salt and water handling.
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Bartter syndrome (BS) is a disease of the kidney tubules that is inherited in an autosomal recessive fashion.
A newborn with BS exhibits the following symptoms:
- polyuria (chronic passage of large volumes of urine),
- abnormally low levels of plasma potassium with metabolic alkalosis,
- excessive levels of calcium in the urine,
- excessive secretions of the hormone, aldosterone,
- elevated levels of renin in the blood, and
- increased urinary prostaglandin E2 excretion.
So far, a causative gene for three BS subtypes (BS1, BS2, BS3) has been discovered. And recently, the location for the gene that causes BS4 (BS syndrome accompanied by sensorineural deafness) was mapped to chromosome 1p31. Ruf, et al., undertook a linkage analysis (an analysis of genes located close to one another on the same gene that tend to be inherited as a unit) on six families with BS4. This analysis brought the researchers closer to being able to identify the gene responsible for BS4.