AQP2 gene mutation C.450T>A in a Tunisian family

Fatma Mnif; Hana Charfi; Fatma Abdelhedi; Malek Bouassida; Faten Haj Kacem Akid; Dhoha Ben Salah; Mouna Mnif; Nadia Charfi; NABILA REKIK MAJDOUB; Mouna Elleuch; Hassen Kammoun; Mohamed Abid

doi:10.1530/endoabs.81.EP696

Introduction: The nephrogenic diabetes insipidus (DI) is an entity to be known. It is essential to know its etiologies and especially its therapeutic modalities which are different from those of the central DI. The familial nature of the disease should suggest a genetic origin. In our paper, we are presenting the case of a Tunisian family with genetic nephrogenic DI.

Case reports: Our family had a history of neglected polyuro-polydipsic syndrome (PPS), delayed growth, deafness, death at an early age and urinary malformations. Our first patient was a 35 years old female. She had a personal history of delayed growth and chronic renal failure. She was suffering from PPS for several years but neglected. A biological workup ruled out simple causes of DI and the water restriction test confirmed its nephrogenic origin. The patient was put on indomethacin with improvement of her symptoms. Her brother, 25-year-old, with a history of deafness and delayed growth, developed a post-traumatic polyuro-polydipsic syndrome evoking the diagnosis of central DI but refuted by the non-improvement of the symptoms after ddVAP. It was the use of the medical records of the sister already known to be a nephrogenic DI carrier that allowed us to correct the diagnosis of central DI. This allowed us to combine indomethacin and thiazide diuretics with improvement of the symptoms. Radiological exploration of the hypothalamic-pituitary region was without abnormality and pituitary hormonal exploration showed hyper gonadotropic hypogonadism and hyperprolactinemia at 39.55 ng/ml. A CT scan with urinary tract revealed a bilateral dilatation of the pyelo-caliceal cavities with no detectable obstruction and a neurologic bladder. The genetic study of the AQP2 and AVPR2 genes was carried out by PCR-sequencing for our patients as well as some relatives. This analysis showed the presence of a homozygous missense mutation in exon 2 of the AQP2 gene in our female patient and in another affected sibling. It is a substitution of a thymine (T) by an adenine (A) at positon 450 of the cDNA: C.450T>A. This mutation was present in the heterozygous state in the mother.

Conclusion: Currently, the use of molecular biology facilitates the management of familial DI with genetic counselling and early detection of the different anomalies before their clinical exacerbation. In our case, the study of this family will incite us to do genetic counseling in its different members and to follow them closely to detect other affected members in time.

Endocrine Abstracts

EP696