Clinical and analytical findings in Gitelman's syndrome associated with homozygosity for the c.1925 G>A SLC12A3 mutation.
BACKGROUND
Gitelman's syndrome (GS) is caused by mutations in the SLC12A3. Most of the mutations are rare, making it difficult to establish a genotype-phenotype correlation. Although GS is a recessive disorder, some patients also have an affected parent, suggesting a dominant inheritance.


METHODS
We sequenced the 26 coding exons of SLC12A3 in a family in which the proband and her father had a late onset GS. We obtained cDNA of the 2 patients and analyzed the effect of a mutation on pre-mRNA splicing.


RESULTS
The 2 patients were homozygous for a nucleotide change in the last nucleotide of exon 15: c.1925 G>A. The mother was a heterozygous carrier for this putative mutation. Amplification of cDNA with primers for exons 14-17 was negative, suggesting that this mutation affected the splicing and promoted mRNA degradation through nonsense-mediated decay.


CONCLUSIONS
We report a family with 2 patients with late onset GS and homozygous for a mutation in the last nucleotide of exon 15. Our study shows that homozygosity for this mutation resulted in a significant loss of normal SLC12A3 transcript.
Coto
Eliecer
E
Genética Molecular, Hospital Universitario Central Asturias (HUCA), Oviedo, Spain. eliecer.coto@sespa.princast.es
Arriba
Gabriel
G
García-Castro
Mónica
M
Santos
Fernando
F
Corao
Ana I
AI
Díaz
Marta
M
Sánchez Heras
Marta
M
Basterrechea
María A
MA
Tallón
Serafín
S
Alvarez
Victoria
V
D000328:Adult; D005260:Female; D053579:Gitelman Syndrome / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011955:Receptors, Drug / Q000235:genetics*; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*
D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters