Open AccessSevere congenital nephrogenic diabetes insipidus in a compound heterozygote with a new large deletion of the AQP2 gene. A case report
Author(s) -
Peces Ramón,
Mena Rocío,
Peces Carlos,
SantosSimarro Fernando,
Fernández Luis,
Afonso Sara,
Lapunzina Pablo,
Selgas Rafael,
Nevado Julián
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.568
Subject(s) - compound heterozygosity , missense mutation , aquaporin 2 , sanger sequencing , nephrogenic diabetes insipidus , multiplex ligation dependent probe amplification , exon , polyuria , medicine , genetics , diabetes insipidus , mutation , endocrinology , biology , gene , diabetes mellitus , mechanical engineering , inlet , water channel , engineering
Background Congenital nephrogenic diabetes insipidus (NDI) is a rare condition characterized by severe polyuria, due to the inability of the kidneys to concentrate urine in response to arginine vasopressin (AVP). In the majority of the cases, the disease shows an X‐linked inherited pattern, although an autosomal recessive inheritance was also observed. Methods We report a patient with a severe NDI diagnosed during the neonatal period. Because the patient was female without a family history of congenital NDI, her disease was thought to exhibit an autosomal recessive form. Results A full mutation analysis of AVP receptor 2 ( AVPR2; MIM#300538) gene showed no mutations. However, direct Sanger sequencing of the aquaporin 2 ( AQP2 ) revealed an apparently homozygous mutation at nucleotide position NM_000486.5:c.374C>T (p.Thr125Met) in exon 2. Further customized multiplex ligation‐dependent probe amplification (MLPA), single‐nucleotide polymorphism (SNP) array analysis, and long‐range polymerase chain reaction (PCR) followed by Sanger sequencing showed a heterozygous exonic deletion comprising exons 2, 3, and partially 4 of AQP2 . Conclusion This is the first case of a compound heterozygote patient with a missense mutation involving NM_000486.5:exon2:c.374C>T (p.Thr125Met) and a gross deletion of at least exons 2, 3, and partially 4 on the AQP2 to present with a severe NDI phenotype.