TY - JOUR
T1 - Founder mutations in the ATP6V1B1 geneexplain most cypriot cases of distal renal tubular acidosis
T2 - First prenatal diagnosis
AU - Elia, Avraam
AU - Voskarides, Konstantinos
AU - Demosthenous, Panayiota
AU - Michalopoulou, Aikaterini
AU - Malliarou, Maria Adamantia
AU - Georgaki, Eleni
AU - Athanasiou, Yiannis
AU - Patsias, Charalambos
AU - Pierides, Alkis
AU - Deltas, Constantinos
PY - 2011/2
Y1 - 2011/2
N2 - Aims: To investigate clinically and genetically all the distal renal tubular acidosis (dRTA) cases in Cyprus, to study one more family from Greece and to perform the first dRTA prenatal diagnosis. We also tried to find any association with sensorineural hearing loss (SNHL) onset and particular mutations. Methods: Nine dRTA families from Cyprus and one from Greece were analyzed for mutations in ATP6V1B1 gene by DNA resequencing and PCR-RFLPs. Clinical diagnosis was performed by standard criteria. Prenatal diagnosis was performed for one Cypriot family. Results: Results show that 7/9 dRTA cases in Cyprus are caused by 229+1G>T and R157C founder mutations in ATP6V1B1 gene. 229+1G>T mutation was estimated to be older than 400 years. No genotype- phenotype correlation was found with SNHL. A known (L81P) and a novel mutation (912delT) were found in the Greek family. Prenatal diagnosis was performed for one Cypriot family, after parents' demand, showing that the embryo was a heterozygous carrier. Conclusion: Existence of only two ATP6V1B1 mutations in the Cypriot population is a diagnostic advantage. The age of onset of SNHL varies in our patients and probably is not related to ATP6V1B1 genotypes. Effective therapy for most of the syndrome symptoms is not satisfactory for some parents who choose prenatal diagnosis to ensure their child's health.
AB - Aims: To investigate clinically and genetically all the distal renal tubular acidosis (dRTA) cases in Cyprus, to study one more family from Greece and to perform the first dRTA prenatal diagnosis. We also tried to find any association with sensorineural hearing loss (SNHL) onset and particular mutations. Methods: Nine dRTA families from Cyprus and one from Greece were analyzed for mutations in ATP6V1B1 gene by DNA resequencing and PCR-RFLPs. Clinical diagnosis was performed by standard criteria. Prenatal diagnosis was performed for one Cypriot family. Results: Results show that 7/9 dRTA cases in Cyprus are caused by 229+1G>T and R157C founder mutations in ATP6V1B1 gene. 229+1G>T mutation was estimated to be older than 400 years. No genotype- phenotype correlation was found with SNHL. A known (L81P) and a novel mutation (912delT) were found in the Greek family. Prenatal diagnosis was performed for one Cypriot family, after parents' demand, showing that the embryo was a heterozygous carrier. Conclusion: Existence of only two ATP6V1B1 mutations in the Cypriot population is a diagnostic advantage. The age of onset of SNHL varies in our patients and probably is not related to ATP6V1B1 genotypes. Effective therapy for most of the syndrome symptoms is not satisfactory for some parents who choose prenatal diagnosis to ensure their child's health.
KW - Cyprus
KW - Distal renal tubular acidosis
KW - Founder mutations
KW - Hellenic population
KW - Mutation dating
KW - Prenatal diagnosis
KW - Sensorineural hearing loss
KW - V-ATPase subunit B1
UR - http://www.scopus.com/inward/record.url?scp=77956082411&partnerID=8YFLogxK
U2 - 10.1159/000320192
DO - 10.1159/000320192
M3 - Article
C2 - 20805693
AN - SCOPUS:77956082411
SN - 1660-2110
VL - 117
SP - c206-c212
JO - Nephron - Clinical Practice
JF - Nephron - Clinical Practice
IS - 3
ER -