A novel splice site mutation of the arginine vasopressin-neurophysin II gene identified in a kindred with autosomal dominant familial neurohypophyseal diabetes insipidus.
Autosomal dominant familial neurohypophyseal diabetes insipidus is an inherited deficiency of arginine vasopressin (AVP), and this is caused by mutations in the AVP-neurophysin II (AVP-NP II) gene. Most of these mutations have been located in the signal peptide or in the NP II moiety. In the present study, we have analyzed the AVP-NP II gene in a Korean family. Clinical and genetic studies were performed on three members of the family, and on a normal healthy unrelated individual. The diagnosis of neurohypophyseal diabetes insipidus was done by performing a fluid deprivation test and a vasopressin challenge. For genetic analysis, the genomic DNA was extracted and the AVP-NP II gene was amplified by polymerase chain reaction (PCR). Clinical assessment of the affected individuals confirmed the diagnosis of neurohypophyseal diabetes insipidus. Genetic analysis of the AVP-NP II gene revealed a novel deletion mutation of a single nucleotide (guanine) within the splice acceptor site of intron 2 (IVS2 +1 delG). The affected individuals were heterozygous for this mutation. We also demonstrated through RT-PCR analysis of the mutant gene that this mutation resulted in the retention of intron 2 during pre-mRNA splicing. We concluded that a novel splicing mutation in the AVP-NP II gene causes neurohypophyseal diabetes insipidus in this family.
Tae
Hyun-Jung
HJ
Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Republic of Korea.
Baek
Ki-Hyun
KH
Shim
Sun-Mi
SM
Yoo
Soon-Jib
SJ
Kang
Moo-Il
MI
Cha
Bong-Yun
BY
Lee
Kwang-Woo
KW
Son
Ho-Young
HY
Kang
Sung-Koo
SK
D000595:Amino Acid Sequence; D001127:Arginine Vasopressin / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D003919:Diabetes Insipidus / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D009154:Mutation; D009481:Neurophysins / Q000235:genetics*; D010375:Pedigree; D010900:Pituitary Diseases / Q000235:genetics*; D012326:RNA Splicing; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D009481:Neurophysins; D001127:Arginine Vasopressin