title: Correlation between clinical phenotypes and X-inactivation patterns in six female carriers with heterozygote vasopressin type 2 receptor gene mutations.
abstract: About 90% of patients with congenital nephrogenic diabetes insipidus (NDI) have vasopressin type 2 receptor (V2R) gene mutations that are inherited in an X-linked recessive manner. Although most female carriers are asymptomatic, some female carriers show polydipsia and polyuria. The reason why female carriers show NDI symptoms is explained by skewed X-inactivation. We studied X-inactivation patterns of six female carriers with heterozygote V2R gene mutations. The X-inactivation pattern in peripheral blood leukocytes was examined using methylation analysis of the polymorphic CAG repeat in the androgen receptor gene. Two asymptomatic female carriers showed random X-inactivation (61.9% and 60.7%). Skewed X-inactivation patterns (71.6%, 79.4%, and 91.2%) occurring preferentially to normal X alleles were recognized in three female carriers who showed clinical NDI symptoms. However, in one female carrier who showed clinical NDI symptoms, random X-inactivation (55.4%) was recognized. In conclusion, the clinical NDI phenotypes may correlate with the X-inactivation patterns in female carriers with heterozygote V2R gene mutations. However, in some female carriers, we cannot predict the clinical phenotypes by the evaluation of the X-inactivation patterns in peripheral blood leukocytes, because X-inactivation ratios within an individual are sometimes different between tissues.
authors.affiliation: First Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Satoh
authors.forename: Sayaka
authors.initials: S
authors.lastname: Ogikubo
authors.forename: Atsuko
authors.initials: A
authors.lastname: Yoshizawa-Ogasawara
mesh_terms: D000328:Adult; D002648:Child; D018500:Diabetes Insipidus, Nephrogenic / Q000097:blood / Q000235:genetics*; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017483:Receptors, Vasopressin / Q000235:genetics* / Q000378:metabolism; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: D017483:Receptors, Vasopressin