Novel mutations associated with nephrogenic diabetes insipidus. A clinical-genetic study

被引：22

作者：

Garcia Castano, Alejandro ^{[1
]}

Perez de Nanclares, Gustavo ^{[1
]}

Madariaga, Leire ^{[2
,3
]}

Aguirre, Mireia ^{[2
]}

Chocron, Sara ^{[4
]}

Madrid, Alvaro ^{[4
]}

Lafita Tejedor, Francisco Javier ^{[5
]}

Gil Campos, Mercedes ^{[6
]}

Sanchez del Pozo, Jaime ^{[7
]}

Ruiz Cano, Rafael ^{[8
]}

Espino, Mar ^{[9
]}

Gomez Vida, Jose Maria ^{[10
]}

Santos, Fernando ^{[11
]}

Garcia Nieto, Victor Manuel ^{[12
]}

Loza, Reyner ^{[13
]}

Miguel Rodriguez, Luis ^{[14
]}

Hidalgo Barquero, Emilia ^{[15
]}

Printza, Nikoleta ^{[16
]}

Antonio Camacho, Juan ^{[17
]}

Castano, Luis ^{[1
,3
,13
,18
]}

Ariceta, Gema ^{[4
,19
]}

机构：

[1] Cruces Univ Hosp, BioCruces Inst, Ciberer, Bizkaia, Spain

[2] Cruces Univ Hosp, Paediat Nephrol, Bizkaia, Spain

[3] Univ Basque Country UPV EHU, Sch Med & Odontol, Dept Paediat, Bizkaia, Spain

[4] Univ Hosp Vall Hebron, Paediat Nephrol, Barcelona, Spain

[5] Complejo Hosp Navarra, Serv Endocrinol, Pamplona, Spain

[6] Reina Sofia Univ Hosp, Paediat Res & Metab Unit, Cordoba, Spain

[7] Hosp 12 Octubre, Div Endocrinol, Dept Paediat, E-28041 Madrid, Spain

[8] Albacete Gen Univ Hosp, Paediat Endocrinol, Albacete, Spain

[9] Hosp 12 Octubre, Paediat Nephrol, E-28041 Madrid, Spain

[10] Motril Hosp, Dept Paediat, Granada, Spain

[11] Asturias Cent Univ Hosp, Paediat Nephrol, Oviedo, Asturias, Spain

[12] Nuestra Senora de Candelaria Univ Hosp, Paediat Nephrol, Tenerife, Canarias, Spain

[13] Cayetano Heredia Univ, Cayetano Heredia Hosp, Nephrol Unit, Lima, Peru

[14] Leon Hosp, Leon, Spain

[15] Materno Infantil Hosp, Dept Paediat Nephrol, Badajoz, Spain

[16] Aristotle Univ Thessaloniki, Dept Paediat, Hippokratio Hosp, GR-54006 Thessaloniki, Greece

[17] St Joan Deu Hosp, Dept Paediat Nephrol, Barcelona, Spain

[18] Ctr Invest Biomed Red Diabet & Enfermedad Metabol, Barcelona, Spain

[19] Autonomous Univ Barcelona, Barcelona, Spain

来源：

EUROPEAN JOURNAL OF PEDIATRICS | 2015年 / 174卷 / 10期

关键词：

Nephrogenic diabetes insipidus; AVPR2; AQP2; Heterozygous females; VASOPRESSIN V2 RECEPTOR; HUMAN ANTIDIURETIC-HORMONE; X-CHROMOSOME INACTIVATION; AVPR2; MUTATIONS; FUNCTIONAL-CHARACTERIZATION; FEMALE CARRIERS; COLLECTING DUCT; WATER CHANNEL; FAMILIES; AQUAPORIN-2;

D O I：

10.1007/s00431-015-2534-4

中图分类号：

R72 [儿科学];

学科分类号：

100202 ;

摘要：

Molecular diagnosis is a useful diagnostic tool in primary nephrogenic diabetes insipidus (NDI), an inherited disease characterized by renal inability to concentrate urine. The AVPR2 and AQP2 genes were screened for mutations in a cohort of 25 patients with clinical diagnosis of NDI. Patients presented with dehydration, polyuria-polydipsia, failure to thrive (mean +/- SD; Z-height -1.9 +/- 2.1 and Z-weight -2.4 +/- 1.7), severe hypernatremia (mean +/- SD; Na 150 +/- 10 mEq/L), increased plasma osmolality (mean +/- SD; 311 +/- 18 mOsm/Kg), but normal glomerular filtration rate. Genetic diagnosis revealed that 24 male patients were hemizygous for 17 different putative disease-causing mutations in the AVPR2 gene (each one in a different family). Of those, nine had not been previously reported, and eight were recurrent. Moreover, we found those same AVPR2 changes in 12 relatives who were heterozygous carriers. Further, in one female patient, AVPR2 gene study turned out to be negative and she was found to be homozygous for the novel AQP2 p.Ala86Val alteration. Conclusion: Genetic analysis presumably confirmed the diagnosis of nephrogenic diabetes insipidus in every patient of the studied cohort. We emphasize that we detected a high presence (50 %) of heterozygous females with clinical NDI symptoms.

引用

页码：1373 / 1385

页数：13

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