Recent advances in our knowledge of pituitary development, acquired mainly from animal models, have enhanced our understanding of the aetiology of isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD), as well as several syndromic forms of growth hormone deficiency (GHD). A number of developmental genes known to be important for organ commitment and cell differentiation and proliferation (HESX1, LHX3, LHX4, PROP1 and PIT1) have been implicated in CPHD with or without other syndromic features. Phenotypes associated with these genetic mutations and their inheritance may be highly variable. Functional analyses of these mutations reveal valuable insights into the function of the proteins and hence into the effect of these mutations on phenotype. Novel insights have been gained into the mechanisms whereby these genes are associated with particular phenotypes as a result of murine transgenesis, e.g. type II autosomal dominant GHD. Mutations within known genes account for a small proportion of cases of IGHD and CPHD, suggesting the role of other as yet unidentified genetic and environmental factors. Hence, genetic testing will in the future have a greater role to play in understanding the mechanisms leading to particular hypopituitary phenotypes and also in predicting the evolution of these disorders. There is, however, no substitute for careful delineation of the phenotype prior to undertaking genetic studies.

Keywords:
Hypopituitarism, Homeobox genes, Combined pituitary hormone deficiency, Growth hormone deficiency, Septo-optic dysplasia
1.
Sheng HZ, Westphal H: Early steps in pituitary organogenesis. Trends Genet 1999;15:236–240.
2.
Burgess R, Lunyak V, Rosenfeld M: Signaling and transcriptional control of pituitary development. Curr Opin Genet Dev 2002;12:534–539.
3.
Dasen JS, Rosenfeld MG: Signaling and transcriptional mechanisms in pituitary development. Annu Rev Neurosci 2001;24:327–355.
4.
Olson LE, Dasen JS, Ju BG, Tollkuhn J, Rosenfeld MG: Paired-like repression/activation in pituitary development. Recent Prog Horm Res 2003;58:249–261.
5.
Scully KM, Rosenfeld MG: Pituitary development: regulatory codes in mammalian organogenesis. Science 2002;295:2231–2235.
6.
Cohen LE, Radovick S: Molecular basis of combined pituitary hormone deficiencies. Endocr Rev 2002;23:431–442.
7.
Dattani MT, Robinson IC: The molecular basis for developmental disorders of the pituitary gland in man. Clin Genet 2000;57:337–346.
8.
Treier M, O’Connell S, Gleiberman A, Price J, Szeto DP, Burgess R, Chuang PT, McMahon AP, Rosenfeld MG: Hedgehog signaling is required for pituitary gland development. Development 2001;128:377–386.
9.
Takuma N, Sheng HZ, Furuta Y, Ward JM, Sharma K, Hogan LM, Pfaff SL, Westphal H, Kimura S, Mahon KA: Formation of Rathke’s pouch requires dual induction from the diencephalon. Development 1998;125:4835–4840.
10.
Thomas PQ, Johnson BV, Rathjen J, Rathjen PD: Sequence, genomic organization, and expression of the novel homeobox gene Hesx1. J Biol Chem 1995;270:3869–3875.
11.
Thomas P, Beddington R: Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo. Curr Biol 1996;6:1487–1496.
12.
Brickman JM, Clements M, Tyrell R, McNay D, Woods K, Warner J, Stewart A, Beddington RS, Dattani MT: Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders. Development 2001;128:5189–5199.
13.
Dasen JS, Barbera JP, Herman TS, Connell SO, Olson L, Ju B, Tollkuhn J, Baek SH, Rose DW, Rosenfeld MG: Temporal regulation of a paired-like homeodomain repressor/TLE corepressor complex and a related activator is required for pituitary organogenesis. Genes Dev 2001;15:3193–3207.
14.
Xu L, Lavinsky RM, Dasen JS, Flynn SE, McInerney EM, Mullen TM, Heinzel T, Szeto D, Korzus E, Kirokawa R, Aggarwal AK, Rose DW, Glass CK, Rosenfeld MG: Signal-specific co-activator domain requirements for Pit-1 activation. Nature 1998;395:301–306.
15.
Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ, O’Connell SM, Gukovsky I, Carriere C, Ryan AK, Miller AP, Zuo L, Glieberman AS, Andersen B, Beamer WG, Rosenfeld MG: Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature 1996;384:327–333.
16.
Gage PJ, Brinkmeier ML, Scarlett LM, Knapp LT, Camper SA, Mahon KA: The Ames dwarf gene, df, is required early in pituitary ontogeny for the extinction of Rpx transcription and initiation of lineage-specific cell proliferation. Mol Endocrinol 1996;10:1570–1581.
17.
Sheng HZ, Zhadanov AB, Mosinger B, Fujii T, Bertuzzi S, Grinberg A, Lee EJ, Huang SP, Mahon K, Westphal H: Specification of pituitary cell lineages by the LIM homeobox gene Lhx3. Science 1996;272:1004–1007.
18.
Dattani MT, Martinez Barbera JP, Thomas PQ, Brickman JM, Gupta R, Martensson IL, Toresson H, Fox M, Wales JK, Hindmarsh PC, Krauss S, Beddington RS, Robinson IC: Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet 1998;19:125–133.
19.
Semina EV, Reiter R, Leysens NJ, Alward WL, Small KW, Datson NA, Siegel-Bartelt J, Bierke-Nelson D, Bitoun P, Zabel BU, Carey JC, Murray JC: Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet 1996;14:392–399.
20.
Gage PJ, Camper SA: Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation. Hum Mol Genet 1997;6:457–464.
21.
Yoshioka H, Meno C, Koshiba K, Sugihara M, Itoh H, Ishimaru Y, Inoue T, Ohuchi H, Semina EV, Murray JC, Murray JC, Hamda H, Noji S: Pitx2, a bicoid-type homeobox gene, is involved in a left-signaling pathway in determination of left-right asymmetry. Cell 1998;94:299–305.
22.
Sheng HZ, Moriyama K, Yamashita T, Li H, Potter SS, Mahon KA, Westphal H: Multistep control of pituitary organogenesis. Science 1997;278:1809–1812.
23.
Dasen JS, O’Connell SM, Flynn SE, Treier M, Gleiberman AS, Szeto DP, Hooshmand F, Aggarwal AK, Rosenfeld MG: Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types. Cell 1999;97:587–598.
24.
Crawford PA, Dorn C, Sadovsky Y, Milbrandt J: Nuclear receptor DAX-1 recruits nuclear receptor corepressor N-CoR to steroidogenic factor 1. Mol Cell Biol 1998;18:2949–2956.
25.
Ikeda Y, Swain A, Weber TJ, Hentges KE, Zanaria E, Lalli E, Tamai KT, Sassone-Corsi P, Lovell-Badge R, Camerino G, Parker KL: Steroidogenic factor 1 and Dax-1 colocalize in multiple cell lineages: potential links in endocrine development. Mol Endocrinol 1996;10:1261–1272.
26.
Ingraham HA, Lala DS, Ikeda Y, Luo X, Shen WH, Nachtigal MW, Rosenfeld MG: The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis. Genes Dev 1994;8:2302–2312.
27.
Zhao L, Bakke M, Krimkevich Y, Cushman LJ, Parlow AF, Camper SA, Simmons DM, Swanson L, Rosenfeld MG: Steroidogenic factor 1 (SF1) is essential for pituitary gonadotrope function. Development 2001;128:147–154.
28.
Andersen B, Pearse RV, Jenne K, Sornson M, Lin SC, Bartke A, Rosenfeld MG: The Ames dwarf gene is required for Pit-1 gene activation. Dev Biol 1995;172:495–503.
29.
Ingraham HA, Chen RP, Mangalam HJ, Elsholtz HP, Flynn SE, Lin CR, Simmons DM, Swanson L, Rosenfeld MG: A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell 1988;55:519–529.
30.
Li S, Crenshaw EB, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG: Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene Pit-1. Nature 1990;347:528–533.
31.
Castrillo JL, Theill LE, Karin M: Function of the homeodomain protein GHF1 in pituitary cell proliferation. Science 1991;253:197–199.
32.
Andersen B, Rosenfeld MG: Pit-1 determines cell types during development of the anterior pituitary gland. A model for transcriptional regulation of cell phenotypes in mammalian organogenesis. J Biol Chem 1994;269:29335–29338.
33.
Holloway JM, Szeto DP, Scully KM, Glass CK, Rosenfeld MG: Pit-1 binding to specific DNA sites as a monomer or dimer determines gene-specific use of a tyrosine-dependent synergy domain. Genes Dev 1995;9:1992–2006.
34.
Jacobson EM, Li P, Leon-del RA, Rosenfeld MG, Aggarwal AK: Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev 1997;11:198–212.
35.
Rhodes SJ, Chen R, DiMattia GE, Scully KM, Kalla KA, Lin SC, Yu VC, Rosenfeld MG: A tissue-specific enhancer confers Pit-1-dependent morphogen inducibility and autoregulation on the Pit-1 gene. Genes Dev 1993;7:913–932.
36.
Parker KL, Hunold JJ, Blethen SL: Septo-optic dysplasia/optic nerve hypoplasia: data from the National Cooperative Growth Study (NCGS). J Pediatr Endocrinol Metab 2002;15(suppl 2):697–700.
37.
Wales JK, Quarrell OW: Evidence for possible Mendelian inheritance of septo-optic dysplasia. Acta Paediatr 1996;85:391–392.
38.
Morishima A, Aranoff GS: Syndrome of septo-optic-pituitary dysplasia: the clinical spectrum. Brain Dev 1986;8:233–239.
39.
Thomas PQ, Dattani MT, Brickman JM, McNay D, Warne G, Zacharin M, Cameron F, Hurst J, Woods K, Dunger D, Stanhope R, Forrest S, Robinson IC, Beddington RS: Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. Hum Mol Genet 2001;10:39–45.
40.
Tajima T, Hattorri T, Nakajima T, Okuhara K, Sato K, Abe S, Nakae J, Fujieda K: Sporadic heterozygous frameshift mutation of HESX1 causing pituitary and optic nerve hypoplasia and combined pituitary hormone deficiency in a Japanese patient. J Clin Endocrinol Metab 2003;88:45–50.
41.
Cohen RN, Cohen LE, Botero D, Yu C, Sagar A, Jurkiewicz M, Radovick S: Enhanced repression by HESX1 as a cause of hypopituitarism and septooptic dysplasia. J Clin Endocrinol Metab 2003;88:4832–4839.
42.
Carvalho LR, Woods KS, Mendonca BB, Marcal N, Zamparini AL, Stifani S, Brickman JM, Arnhold IJ, Dattani MT: A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction. J Clin Invest 2003;112:1192–1201.
43.
Netchine I, Sobrier ML, Krude H, Schnabel D, Maghnie M, Marcos E, Duriez B, Cacheux V, Moers A, Goossens M, Gruters A, Amselem S: Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency. Nat Genet 2000;25:182–186.
44.
Machinis K, Pantel J, Netchine I, Léger J, Camand OJ, Sobrier ML, Dastot-Le-Moal F, Abitbol M, Czernichow P, Amselem S: Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4. Am J Hum Genet 2001;69:961–968.
45.
Roessler E, Du YZ, Mullor JL, Casas E, Allen WP, Gillessen-Kaesbach G, Roeder ER, Ming JE, Ruiz Altaba A, Muenke M: Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features. Proc Natl Acad Sci USA 2003;100:13424–13429.
46.
Tatsumi K, Miyai K, Notomi T, Kaibe K, Amino N, Mizuno Y, Kohno H: Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene. Nat Genet 1992;1:56–58.
47.
Pfäffle RW, DiMattia GE, Parks JS, Brown MR, Wit JM, Jansen M, Van der Nat H, Van den Brande L, Rosenfeld MG, Ingraham HA: Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia. Science 1992;257:1118–1121.
48.
Pfäffle RW, Martinez R, Kim C, Frisch H, Lebl J, Otten B, Heimann G: GH and TSH deficiency. Exp Clin Endocrinol Diabetes 1997;105(suppl 4):1–5.
49.
Radovick S, Nations M, Du Y, Berg LA, Weintraub BD, Wondisford FE: A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency. Science 1992;257:1115–1118.
50.
Radovick S, Cohen LE, Wondisford FE: The molecular basis of hypopituitarism. Horm Res 1998;49(suppl 1):30–36.
51.
Cogan JD, Wu W, Phillips JA, Arnhold IJ, Agapito A, Fofanova OV, Osorio MG, Bircan I, Moreno A, Mendonca BB: The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. J Clin Endocrinol Metab 1998;83:3346–3349.
52.
Pfäffle RW, Blankenstein O, Wuller S, Kentrup H: Combined pituitary hormone deficiency: role of Pit-1 and Prop-1. Acta Paediatr Suppl 1999;88:33–41.
53.
Wu W, Cogan JD, Pfäffle RW, Dasen JS, Frisch H, O’Connell SM, Flynn SE, Brown MR, Mullis PE, Parks JS, Phillips JA 3rd, Rosenfeld MG: Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genet 1998;18:147–149.
54.
Deladoey J, Fluck C, Buyukgebiz A, Kuhlmann BV, Eble A, Hindmarsh PC, Wu W, Mullis PE: ‘Hot spot’ in the PROP1 gene responsible for combined pituitary hormone deficiency. J Clin Endocrinol Metab 1999;84:1645–1650.
55.
Arroyo A, Pernasetti F, Vasilyev VV, Amato P, Yen SS, Mellon PL: A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty. Clin Endocrinol (Oxf) 2002;57:283–291.
56.
Parks JS, Brown MR, Hurley DL, Phelps CJ, Wajnrajch MP: Heritable disorders of pituitary development. J Clin Endocrinol Metab 1999;84:4362–4370.
57.
Agarwal G, Bhatia V, Cook S, Thomas PQ: Adrenocorticotropin deficiency in combined pituitary hormone deficiency patients homozygous for a novel PROP1 deletion. J Clin Endocrinol Metab 2000;85:4556–4561.
58.
Pernasetti F, Toledo SP, Vasilyev VV, Hayashida CY, Cogan JD, Ferrari C, Lourenco DM, Mellon PL: Impaired adrenocorticotropin-adrenal axis in combined pituitary hormone deficiency caused by a two-base pair deletion (301–302delAG) in the prophet of Pit-1 gene. J Clin Endocrinol Metab 2000;85:390–397.
59.
Asteria C, Oliveira JH, Abucham J, Beck-Peccoz P: Central hypocortisolism as part of combined pituitary hormone deficiency due to mutations of PROP-1 gene. Eur J Endocrinol 2000;143:347–352.
60.
Mendonca BB, Osorio MG, Latronico AC, Estefan V, Lo LS, Arnhold IJ: Longitudinal hormonal and pituitary imaging changes in two females with combined pituitary hormone deficiency due to deletion of A301,G302 in the PROP1 gene. J Clin Endocrinol Metab 1999;84:942–945.
61.
Solomon NM, Nouri S, Warne GL, Lagerstrom-Fermer M, Forrest SM, Thomas PQ: Increased gene dosage at Xq26–q27 is associated with X-linked hypopituitarism. Genomics 2002;79:553–559.
62.
Procter AM, Phillips JA, Cooper DN: The molecular genetics of growth hormone deficiency. Hum Genet 1998;103:255–272.
63.
Illig R: Growth hormone antibodies in patients treated with different preparations of human growth hormone (HGH). J Clin Endocrinol Metab 1970;31:679–688.
64.
Phillips JA III, Hjelle BL, Seeburg PH, Zachmann M: Molecular basis for familial isolated growth hormone deficiency. Proc Natl Acad Sci USA 1981;78:6372–6375.
65.
Wajnrajch MP, Gertner JM, Harbison MD, Chua SC Jr, Leibel RL: Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat Genet 1996;12:88–90.
66.
Carakushansky M, Whatmore AJ, Clayton PE, Shalet SM, Gleeson HK, Price DA, Levene MA, Salvatori R: A new missense mutation in the growth hormone-releasing hormone receptor gene in familial isolated GH deficiency. Eur J Endocrinol 2003;148:25–30.
67.
McGuinness L, Magoulas C, Sesay AK, Mathers K, Carmignac D, Manneville JB, Christian H, Phillips JA 3rd, Robinson IC: Autosomal dominant growth hormone deficiency disrupts secretory vesicles in vitro and in vivo in transgenic mice. Endocrinology 2003;144:720–731.
68.
Moseley CT, Mullis PE, Prince MA, Phillips JA III: An exon splice enhancer mutation causes autosomal dominant GH deficiency. J Clin Endocrinol Metab 2002;87:847–852.
69.
Mullis PE, Deladoey J, Dannies PS: New GH-1 gene mutations: expanding the spectrum of causes of isolated growth hormone deficiency. J Pediatr Endocrinol Metab 2002;15(suppl 5):1301–1310.
70.
Laumonnier F, Ronce N, Hamel BC, Thomas P, Lespinasse J, Raynaud M, Paringaux C, Van-Bokhoven H, Kalscheuer V, Fryns JP, Chelly J, Moraine C, Briault S: Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency. Am J Hum Genet 2002;71:1450–1455.
71.
Collu R, Tang J, Castagne J, Lagace G, Masson N, Huot C, Deal C, Delvin E, Faccenda E, Eidna KA, Van Vliet G: A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin-releasing hormone receptor gene. J Clin Endocrinol Metab 1997;82:1561–1565.
72.
Dacou-Voutetakis C, Feltquate DM, Drakopoulou M, Kourides IA, Dracopoli NC: Familial hypothyroidism caused by a nonsense mutation in the thyroid-stimulating hormone beta-subunit gene. Am J Hum Genet 1990;46:988–993.
73.
Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A: Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 1998;19:155–157.
74.
Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L, Montague CT, Hutton JC, O’Rahilly S: Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 1997;16:303–306.
75.
O’Rahilly S, Gray H, Humphreys PJ, Krook A, Polonsky KS, White A, Gibson S, Taylor K, Carr C: Impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med 1995;333:1386–1390.
76.
Jackson RS, Creemers JW, Farooqi IS, Raffin-Sanson ML, Varro A, Dockray GJ, Holst JJ, Brubaker PL, Corvol P, Polonsky KS, Ostrega D, Becker KL, Bertagna X, Hutton JC, White A, Dattani MT, Hussain K, Middleton SJ, Nicole TM, Milla PJ, Lindley KJ, O’Rahilly S: Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest 2003;112:1550–1560.
77.
Lamolet B, Pulichino A, Lamonerie T, Gauthier Y, Brue T, Enjalbert A, Drouin J: A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins. Cell 2001;104:849–859.
78.
Fromantin M, Gineste J, Didier A, Rouvier J: Impuberism and hypogonadism at induction into military service. Statistical study. Probl Actuels Endocrinol Nutr 1973;16:179–199.
79.
Filippi G: Klinefelter’s syndrome in Sardinia. Clinical report of 265 hypogonadic males detected at the time of military check-up. Clin Genet 1986;30:276–284.
80.
Muñoz A, Dieguez E: A plea for proper recognition: the syndrome of Maestre de San Juan-Kallmann. Am J Neuroradiol 1997;18:1395–1396.
81.
Bick DP, Ballabio A: Bringing Kallmann syndrome into focus. Am J Neuroradiol 1993;14:852–854.
82.
Hardelin JP, Levilliers J, Blanchard S, Carel JC, Leutenegger M, Pinard-Bertelletto JP Bouloux P, Petit C: Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome. Hum Mol Genet 1993;2:373–377.
83.
Dode C, Levilliers J, Dupont JM, De Paepe A, Le Du N, Soussi-Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pacheux C, Le Tessier D, Cruaud C, Delpech M, Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP: Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet 2003;33:463–465.
84.
Tabarin A: Congenital adrenal hypoplasia and DAX-1 gene mutations. Ann Endocrinol (Paris) 2001;62:202–206.
85.
de Roux N, Milgrom E: Inherited disorders of GnRH and gonadotropin receptors. Mol Cell Endocrinol 2001;179:83–87.
86.
de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E: Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA 2003;100:10972–10976.
87.
Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O’Rahilly S: Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997;387:903–908.
88.
Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Leboue Y, Froguel P, Guy-Grand B: A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998;392:398–401.
89.
Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O’Rahilly S: Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999;341:879–884.
90.
Ito M, Mori Y, Oiso Y, Saito H: A single base substitution in the coding region for neurophysin II associated with familial central diabetes insipidus. J Clin Invest 1991;87:725–728.
91.
Ito M, Jameson JL, Ito M: Molecular basis of autosomal dominant neurohypophyseal diabetes insipidus. Cellular toxicity caused by the accumulation of mutant vasopressin precursors within the endoplasmic reticulum. J Clin Invest 1997;99:1897–1905.
92.
Ito M, Yu RN, Jameson JL: Mutant vasopressin precursors that cause autosomal dominant neurohypophyseal diabetes insipidus retain dimerization and impair the secretion of wild-type proteins. J Biol Chem 1999;274:9029–9037.
93.
Willcutts MD, Felner E, White PC: Autosomal recessive familial neurohypophyseal diabetes insipidus with continued secretion of mutant weakly active vasopressin. Hum Mol Genet 1999;8:1303–1307.
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