BACKGROUNDAs an X-linked recessive way, arginine vasopressin receptor 2 (AVPR2) gene mutation resulted in a hereditary disease - congenital nephrogenic diabetes insipidus (CNDI). We found a suspect clinical CNDI pedigree. In order to identify the genetic etiology, we performed the genetic analysis.

METHODSThe clinical features of the proband and his family members were recorded. The laboratory tests and imaging inspections were analyzed. The water deprivation and pituitrin loading test were performed in the proband and his brother. The genomic DNA of all the members of the pedigree was extracted and then PCR amplification on AVPR2 gene was carried out. Sequencing in both directions was performed to identify mutation on AVPR2 gene.

RESULTSBoth the proband and his brother were diagnosed as CNDI, meanwhile the other members of this pedigree were normal. No severe biochemical abnormality was found in the two CNDI patients. Both the patients had moderate urinary retention, severe megaloureter and hydronephrosis, and mild renal insufficiency. Two mutations of AVPR2 gene were discovered in the 3rd exon in the patients, a silent mutation L309L and a nonsense mutation R337X. The AVPR2 gene R337X mutation was co-segregated with CNDI. R337X mutation was not a reported mutation in the mainland of China.

CONCLUSIONThe AVPR2 gene R337X mutation was also a genetic etiology of CNDI patients in the mainland of China.

Adult ; Diabetes Insipidus, Nephrogenic ; genetics ; Female ; Humans ; Male ; Mutation ; Pedigree ; Receptors, Vasopressin ; genetics ; Vasopressins ; genetics

OBJECTIVE: To detect potential variant in a male neonate affected with congenital nephrogenic diabetes insipidus (CNDI). METHODS: Clinical data of the patient was collected. Genomic DNA was extracted from peripheral blood samples from the child and his parents. The whole coding regions of the arginine vasopressin V2 receptor (AVPR2) gene were amplified by PCR and subjected to Sanger sequencing. RESULTS: The patient presented recurrent fever and polyuria after birth. Multiple blood gas analyses indicated hypernatremia. Ultrasound showed bilateral hydronephrosis and hydroureter. The patient was partially responsive to hydrochlorothiazide. DNA analysis identified a hemizygous frameshift variant c.890-899delACCCGGAGGC in exon 2 of the AVPR2 gene in the proband. His mother was heterozygous for the same variant. CONCLUSION The c.890-899delACCCGGAGGC variant of the AVPR2 gene probably underlies the CNDI in the child. Above discovery has enriched to spectrum of CNDI associated variants.
Adult ; Diabetes Insipidus, Nephrogenic/genetics* ; Exons ; Female ; Frameshift Mutation ; Humans ; Hydrochlorothiazide/therapeutic use* ; Infant, Newborn ; Male ; Pedigree ; Receptors, Vasopressin/genetics*

OBJECTIVE: To explore the clinical characteristics, genetic basis and clinical treatment of seven neonates with congenital nephrogenic diabetes insipidus (NDI). METHODS: Clinical data of the patients were collected. High-throughput sequencing was carried out to detect potential variants. Sanger sequencing was used to verify the results. RESULTS: The patients were all males, with the age of onset being 10 to 21 days. All patients were admitted to the hospital for intermittent fever as the first symptom during the neonatal period. Additional symptoms had included polydipsia and polyuria. After the treatment, 5 patients had recovered, the remainders still had NDI symptoms and developmental retardation. Five children were found to harbor pathogenic variants of the AVPR2/AQP2 gene, which included one in-frame mutation of c.645_646insGCACCTACCCTGGGTATCGCC, two missense mutations of c.541C>T and c.419C>A, and two hemizygous deletions of the AVPR2/AQP2 gene. Among these, two were unreported previously. Cases 6 and 7 were a pair of twins. Both had carried homozygous missense variants of c.538G>A of the AVPR2/AQP2 gene, which was known to be pathogenic. CONCLUSION AVPR2/AQP2 is the main pathogenic gene for congenital NDI, for which two novel pathogenic variants have been discovered in this study. Above results have provided a basis for clinical diagnosis and genetic counseling for the affected pedigrees.
Aquaporin 2/genetics* ; Child ; Diabetes Insipidus, Nephrogenic/genetics* ; Diabetes Mellitus ; Humans ; Infant, Newborn ; Male ; Molecular Biology ; Mutation ; Pedigree ; Receptors, Vasopressin/genetics*

Most cases of hydronephrosis are caused by urinary tract obstruction. However, excessive polyuric syndrome rarely gives rise to non-obstructive hydronephrosis, megaureter, and a distended bladder. The authors report here on two cases of congenital nephrogenic diabetes insipidus (NDI) with severe bilateral hydronephrosis and megaureter. It is Interesting that the patients were symptomless except for their polyuria, and they both presented with bilateral hydronephrosis. Fluid deprivation testing revealed the presence of AVP resistant NDI. Gene analysis for these patients showed the AVP receptor 2 (V2R) missense mutations (Q225X and S126F), which have previously been reported on in other studies. We made the diagnosis of NDI by using a physiologic test, and we confirmed it by mutation analysis of the V2R gene.
Receptors, Vasopressin/*genetics ; Polyuria/complications/diagnosis/genetics ; Mutation, Missense ; Male ; Hydronephrosis/complications/*diagnosis/genetics ; Humans ; Diabetes Insipidus, Nephrogenic/complications/*diagnosis/genetics ; DNA Mutational Analysis ; Adult

OBJECTIVETo detect potential mutation in a pedigree affected with congenital nephrogenic diabetes insipidus (NDI).

METHODSClinical data of a male patient affected with NDI was collected. Genomic DNA was extracted from peripheral blood samples from the patient and five family members. The whole coding region of the arginine vasopressin receptor 2 (AVPR2) gene was amplified by PCR and directly sequenced.

RESULTSThe patient presented polyuria and polydipsia postnatally. Computerized tomography revealed bilateral hydronephrosis and hydroureter. The patient was responsive to hydrochlorothiazide but not to desmopressin. DNA analysis identified a hemizygous missence mutation c.295 T>C in exon 2 of the AVPR2 gene in the proband. His mother and grandmother were both heterozygous for the same mutation.

CONCLUSIONThe congenital NDI in the patient was probably due to mutation of the AVPR2 gene.

Adolescent ; Base Sequence ; DNA Mutational Analysis ; Diabetes Insipidus, Nephrogenic ; congenital ; genetics ; Exons ; genetics ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Mutation ; Pedigree ; Receptors, Vasopressin ; genetics

Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. There are three inheritance patterns of CNDI: the X-linked recessive form associated with vasopressin V2 receptor gene mutations, and the autosomal recessive and dominant forms associated with aquaporin-2 gene (AQP2) mutations. The evaluation for polyuria and polydipsia in a one-month-old Korean girl revealed no response to vasopressin and confirmed the diagnosis of CNDI. Because the child was female without family history of CNDI, her disease was thought to be an autosomal recessive form. We analyzed the AQP2 gene and detected a compound heterozygous missense point mutation: (70)Ala (GCC) to Asp (GAC) in exon 1 inherited from her father and (187)Arg (CGC) to His (CAC) in exon 3 inherited from her mother. The first mutation is located within the first NPA motif of the AQP2 molecule and the second one right after the second NPA motif. This is the first report to characterize AQP2 mutations in Korean patients with autosomal recessive CNDI, and expands the spectrum of AQP2 mutations by reporting two novel mutation, (70)Ala (GCC) to Asp (GAC) and (187)Arg (CGC) to His (CAC).
Aquaporin 2/*genetics ; Base Sequence ; Child, Preschool ; DNA/genetics ; DNA Mutational Analysis ; Diabetes Insipidus, Nephrogenic/congenital/*genetics ; Female ; Genes, Recessive ; Heterozygote ; Humans ; Infant ; Male ; Mutation, Missense ; Point Mutation ; Research Support, Non-U.S. Gov't

No abstract available.
Adult ; DNA Mutational Analysis ; Diabetes Insipidus, Nephrogenic/*complications/diagnosis/genetics/therapy ; Disease Progression ; Genetic Predisposition to Disease ; Humans ; Kidney Failure, Chronic/diagnosis/*etiology ; Male ; Mutation ; Phenotype ; Receptors, Vasopressin/genetics ; Renal Dialysis ; Tomography, X-Ray Computed

Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases.
Ataxia ; Bartter Syndrome ; Brugada Syndrome ; Cardiovascular System ; Channelopathies* ; Diabetes Insipidus, Nephrogenic ; Diabetes Mellitus ; Endocrine System ; Epilepsy, Generalized ; Genetics ; Hypoglycemia ; Hypokalemic Periodic Paralysis ; Immune System ; Ion Channels ; Isaacs Syndrome ; Long QT Syndrome ; Membranes ; Migraine with Aura ; Myasthenia Gravis ; Nervous System ; Neuromyelitis Optica ; Organelles ; Polycystic Kidney Diseases ; Respiratory System ; Seizures, Febrile