Mutation of Glu78 of the AVP-NPII gene impairs neurophysin as a carrier protein for arginine vasopressin in a family with neurohypophyseal diabetes insipidus.
Familial neurohypophyseal diabetes insipidus (FNDI; OMIM 192340) is a rare inherited disorder with an autosomal dominant inheritance pattern. It is characterized by persistent polydipsia and polyuria induced by deficient or absent secretion of arginine vasopressin (AVP). We report a Korean kindred in whom FNDI is associated with a novel deletion mutation in exon 2 of the AVP-NPII gene encoding the neurophysin II moiety. An 18-yr-old man with polyuria and polydipsia was shown to have central diabetes insipidus by using the water deprivation test. Four family members were suspected to have symptomatic vasopressin-deficient diabetes insipidus. Direct sequencing of the AVP-NPII gene showed a heterozygous GAG deletion mutation in exon 2, which results in in-frame deletion of glutamic acid (c.232_234delGAG; p.Glu78del). The mutation was predicted to yield an abnormal AVP precursor lacking Glu78 (E78) in its neurophysin II moiety. Because Glu78 is essential for neurophysin II molecules to form a salt bridge with AVP, the function of neurophysin as a carrier protein for AVP would be impaired. The proband's mother and sister have the same mutation. Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the appropriate expression of vasopressin.
Lee
Yong-Wha
YW
Department of Laboratory Medicine, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon 420-767, South Korea.
Lee
Kyung Wook
KW
Ryu
Ji Won
JW
Mok
Ji Oh
JO
Ki
Chang-Seok
CS
Park
Hyeong Kyu
HK
Kim
Yeo Joo
YJ
Kim
Sang Jin
SJ
Byun
Dong Won
DW
Suh
Kyo Ill
KI
Yoo
Myung Hi
MH
Shin
Hee Bong
HB
Lee
You Kyoung
YK
Kim
Chul-Hee
CH
D000293:Adolescent; D000595:Amino Acid Sequence; D001127:Arginine Vasopressin / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D004252:DNA Mutational Analysis; D020790:Diabetes Insipidus, Neurogenic / Q000235:genetics*; D005190:Family; D005260:Female; D018698:Glutamic Acid / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009481:Neurophysins / Q000235:genetics*; D010375:Pedigree; D014868:Water Deprivation
D002352:Carrier Proteins; D009481:Neurophysins; D001127:Arginine Vasopressin; D018698:Glutamic Acid