Six novel mutations in the arginine vasopressin gene in 15 kindreds with autosomal dominant familial neurohypophyseal diabetes insipidus give further insight into the pathogenesis

被引:36
作者
Christensen, JH
Siggaard, C
Corydon, TJ
DeSanctis, L
Kovacs, L
Robertson, GL
Gregersen, N
Rittig, S
机构
[1] Aarhus Univ Hosp, Dept Pediat, Skejby Sygehus, DK-8200 Aarhus, Denmark
[2] Aarhus Univ Hosp, Pediat Res Lab, Skejby Sygehus, DK-8200 Aarhus, Denmark
[3] Univ Aarhus, Dept Human Genet, Aarhus, Denmark
[4] Univ Turin, Dept Pediat, Turin, Italy
[5] Comenius Univ, Comenius Univ Med Sch, Bratislava, Slovakia
[6] Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA
[7] Aarhus Univ Hosp, Res Unit Mol Med, Skejby Sygehus, DK-8200 Aarhus, Denmark
关键词
diabetes insipidus; AVP gene; mutation; neurohypophyseal; autosomal dominant; neurophysin II;
D O I
10.1038/sj.ejhg.5201086
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by postnatal arginine vasopressin (AVP) deficiency resulting from mutations in the AVP gene encoding the AVP preprohormone. To advance the understanding of adFNDI further, we have searched for mutations in the AVP gene in 15 unrelated kindreds in which diabetes insipidus appeared to be segregating. In nine kindreds, seven different previously described mutations were identified. In each of the other six kindreds, unique novel mutations were identified. Two of these (225A>G and 227G>A) change a nucleotide in the translation initiation codon of the signal peptide, whereas the other four (1797T>C, 1884G>A, 1907T>G, and 2112C>G) predict amino-acid substitutions in the neurophysin II moiety of the AVP prohormone, namely V67A (NP36), G96D (NP65), C104G (NP73), and C116W (NP85). Among these, the mutation predicting the V67A ( NP36) substitution is remarkable. It affects a region of the neurophysin II not affected by any other mutations, produces only a minor change, and its inheritance suggests an incomplete penetrance. Our findings both confirm and further extend the mutation pattern that has emerged in adFNDI, suggesting that the mutations affect amino-acid residues known or reasonably presumed to be important for the proper folding and/or dimerization of the neurophysin II moiety of the AVP prohormone.
引用
收藏
页码:44 / 51
页数:8
相关论文
共 57 条
[1]  
Abbes AP, 2000, CLIN CHEM, V46, P1699
[2]  
Antonarakis SE, 1998, HUM MUTAT, V11, P1
[3]   HEREDITARY DIABETES-INSIPIDUS - AN IMMUNOHISTOCHEMICAL STUDY OF THE HYPOTHALAMUS AND PITUITARY-GLAND [J].
BERGERON, C ;
KOVACS, K ;
EZRIN, C ;
MIZZEN, C .
ACTA NEUROPATHOLOGICA, 1991, 81 (03) :345-348
[4]   Mechanism of endoplasmic reticulum retention of mutant vasopressin precursor caused by a signal peptide truncation associated with diabetes insipidus [J].
Beuret, N ;
Rutishauser, J ;
Bider, MD ;
Spiess, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (27) :18965-18972
[5]   A signal peptide mutation of the arginine vasopressin gene in monozygotic twins [J].
Boson, WL ;
Sarubi, JC ;
d'Alva, CB ;
Friedman, E ;
Faria, D ;
De Marco, L ;
Wajchenberg, B .
CLINICAL ENDOCRINOLOGY, 2003, 58 (01) :108-110
[6]   HEREDITARY IDIOPATHIC DIABETES INSIPIDUS - A CASE REPORT WITH AUTOPSY FINDINGS [J].
BRAVERMAN, LE ;
MANCINI, JP ;
MCGOLDRICK, DM .
ANNALS OF INTERNAL MEDICINE, 1965, 63 (03) :503-+
[7]   STRUCTURE AND FOLDING PROPERTIES OF NEUROPHYSIN AND ITS PEPTIDE COMPLEXES - BIOLOGICAL IMPLICATIONS [J].
BRESLOW, E .
REGULATORY PEPTIDES, 1993, 45 (1-2) :15-19
[8]  
BRESLOW E, 1990, ADV ENZYMOL RAMB, V63, P1
[9]   Identification of a novel mutation in the arginine vasopressin-neurophysin II gene in familial central diabetes insipidus [J].
Bullmann, C ;
Kotzka, J ;
Grimm, T ;
Heppner, C ;
Jockenhövel, F ;
Krone, W ;
Müller-Wieland, D .
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 2002, 110 (03) :134-137
[10]   Identification of a novel nonsense mutation and a missense substitution in the vasopressin-neurophysin II gene in two Spanish kindreds with familial neurohypophyseal diabetes insipidus [J].
Calvo, B ;
Bilbao, JR ;
Urrutia, I ;
Eizaguirre, J ;
Gaztambide, S ;
Castaño, L .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (03) :995-997