Pituitary transcription factors in the aetiology of combined pituitary hormone deficiency

Pfaffle, 2006, Genetics of growth in the normal child, European Journal of Endocrinology, 155, S27, 10.1530/eje.1.02234 Savage, 2003, Transcriptional control during mammalian anterior pituitary development, Gene, 319, 1, 10.1016/S0378-1119(03)00804-7 Zhu, 2007, Molecular physiology of pituitary development: signaling and transcriptional networks, Physiological Reviews, 87, 933, 10.1152/physrev.00006.2006 Franca, 2010, Novel heterozygous nonsense GLI2 mutations in patients with hypopituitarism and ectopic posterior pituitary lobe without holoprosencephaly, Journal of Clinical Endocrinology and Metabolism, 10.1210/jc.2010-1050 Roessler, 2003, Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features, Proceedings of the National Academy of Sciences of the United States of America, 100, 13424, 10.1073/pnas.2235734100 Douchi, 2001, A woman with isolated prolactin deficiency, Acta Obstetricia et Gynecologica Scandinavica, 80, 368 Lania, 2008, Central hypothyroidism, Pituitary, 11, 181, 10.1007/s11102-008-0122-6 Trarbach, 2007, Genetic insights into human isolated gonadotropin deficiency, Pituitary, 10, 381, 10.1007/s11102-007-0061-7 Yamada, 2008, Mechanisms related to the pathophysiology and management of central hypothyroidism, Nature Clinical Practice Endocrinology and Metabolism, 4, 683, 10.1038/ncpendmet0995 Krude, 1998, Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans, Nature Genetics, 19, 155, 10.1038/509 Krude, 2003, Obesity due to proopiomelanocortin deficiency: three new cases and treatment trials with thyroid hormone and ACTH4-10, Journal of Clinical Endocrinology and Metabolism, 88, 4633, 10.1210/jc.2003-030502 Lee, 2006, A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance, Cell Metabolism, 3, 135, 10.1016/j.cmet.2006.01.006 Lamolet, 2001, A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins, Cell, 104, 849, 10.1016/S0092-8674(01)00282-3 Vallette-Kasic, 2005, Congenital isolated adrenocorticotropin deficiency: an underestimated cause of neonatal death, explained by TPIT gene mutations, Journal of Clinical Endocrinology and Metabolism, 90, 1323, 10.1210/jc.2004-1300 Sornson, 1996, Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism, Nature, 384, 327, 10.1038/384327a0 Bottner, 2004, PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis, Journal of Clinical Endocrinology and Metabolism, 89, 5256, 10.1210/jc.2004-0661 Vieira, 2007, Molecular analysis of PROP1, PIT1, HESX1, LHX3, and LHX4 shows high frequency of PROP1 mutations in patients with familial forms of combined pituitary hormone deficiency, Arquivos Brasileiros de Endocrinologia, 51, 1097, 10.1590/S0004-27302007000700012 Blum WF, Shavrikova EP, Sampson C, et al. Screening of a large cohort of pediatric patients with GH deficiency for mutations in genes involved in the regulation of pituitary development and GH secretion. 49th Annual ESPE Meeting, Prague; 2010. FC4–95. Arroyo, 2002, A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty, Clinical Endocrinology (Oxford), 57, 283, 10.1046/j.1365-2265.2002.01550.x Reynaud, 2005, An uncommon phenotype with familial central hypogonadism caused by a novel PROP1 gene mutant truncated in the transactivation domain, Journal of Clinical Endocrinology and Metabolism, 90, 4880, 10.1210/jc.2005-0119 Nakamura, 1999, Prop-1 gene expression in human pituitary tumors, Journal of Clinical Endocrinology and Metabolism, 84, 2581, 10.1210/jc.84.7.2581 do Amaral, 2007, Combined pituitary hormone deficiency and PROP-1 mutation in two siblings: a distinct MR imaging pattern of pituitary enlargement, American Journal of Neuroradiology, 28, 1369, 10.3174/ajnr.A0545 Riepe, 2001, Longitudinal imaging reveals pituitary enlargement preceding hypoplasia in two brothers with combined pituitary hormone deficiency attributable to PROP1 mutation, Journal of Clinical Endocrinology and Metabolism, 86, 4353, 10.1210/jc.86.9.4353 Turton, 2005, Mutations within the transcription factor PROP1 are rare in a cohort of patients with sporadic combined pituitary hormone deficiency (CPHD), Clinical Endocrinology (Oxford), 63, 10, 10.1111/j.1365-2265.2005.02291.x Voutetakis, 2004, Pituitary magnetic resonance imaging in 15 patients with Prop1 gene mutations: pituitary enlargement may originate from the intermediate lobe, Journal of Clinical Endocrinology and Metabolism, 89, 2200, 10.1210/jc.2003-031765 Nasonkin, 2004, Pituitary hypoplasia and respiratory distress syndrome in Prop1 knockout mice, Human Molecular Genetics, 13, 2727, 10.1093/hmg/ddh311 Ward, 2005, Role of PROP1 in pituitary gland growth, Molecular Endocrinology, 19, 698, 10.1210/me.2004-0341 Ward, 2006, Cell proliferation and vascularization in mouse models of pituitary hormone deficiency, Molecular Endocrinology, 20, 1378, 10.1210/me.2005-0409 Deladoey, 1999, “Hot spot” in the PROP1 gene responsible for combined pituitary hormone deficiency, Journal of Clinical Endocrinology and Metabolism, 84, 1645, 10.1210/jc.84.5.1645 Fluck, 1998, Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg→Cys at codon 120 (R120C), Journal of Clinical Endocrinology and Metabolism, 83, 3727, 10.1210/jc.83.10.3727 Pernasetti, 2000, 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, Journal of Clinical Endocrinology and Metabolism, 85, 390, 10.1210/jc.85.1.390 Vallette-Kasic, 2001, PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency, Journal of Clinical Endocrinology and Metabolism, 86, 4529, 10.1210/jc.86.9.4529 Duquesnoy, 1998, Human Prop-1: cloning, mapping, genomic structure. Mutations in familial combined pituitary hormone deficiency, FEBS Letters, 437, 216, 10.1016/S0014-5793(98)01234-4 Kelberman, 2009, Molecular analysis of novel PROP1 mutations associated with combined pituitary hormone deficiency (CPHD), Clinical Endocrinology (Oxford), 70, 96, 10.1111/j.1365-2265.2008.03326.x Georgopoulos, 2006, Long-term follow-up of combined pituitary hormone deficiency in two siblings with a Prophet of Pit-1 gene mutation, Gynecology and Endocrinology, 22, 704, 10.1080/09513590601030290 Parks, 1999, Heritable disorders of pituitary development, Journal of Clinical Endocrinology and Metabolism, 84, 4362, 10.1210/jc.84.12.4362 Tang, 1993, Gonadotropin secretion, synthesis, and gene expression in human growth hormone transgenic mice and in Ames dwarf mice, Endocrinology, 132, 2518, 10.1210/en.132.6.2518 Raetzman, 2006, Persistent expression of Notch2 delays gonadotrope differentiation, Molecular Endocrinology, 20, 2898, 10.1210/me.2005-0394 Olson, 2006, Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination, Cell, 125, 593, 10.1016/j.cell.2006.02.046 Salisbury, 2008, Welcoming beta-catenin to the gonadotropin-releasing hormone transcriptional network in gonadotropes, Molecular Endocrinology, 22, 1295, 10.1210/me.2007-0515 de Graaff, 2009, Genetic screening of a Dutch population with isolated GH deficiency (IGHD), Clinical Endocrinology (Oxford), 70, 742, 10.1111/j.1365-2265.2008.03414.x Laron, 2004, Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958–2003, Journal of Clinical Endocrinology and Metabolism, 89, 1031, 10.1210/jc.2003-031033 Bartke, 1965, The response of two types of dwarf mice to growth hormone, thyrotropin, and thyroxine, General and Comparative Endocrinology, 5, 418, 10.1016/0016-6480(65)90102-4 Simmons, 1990, Pituitary cell phenotypes involve cell-specific Pit-1 mRNA translation and synergistic interactions with other classes of transcription factors, Genes and Devlopment, 4, 695, 10.1101/gad.4.5.695 Kerr, 2008, Basic science and clinical research advances in the pituitary transcription factors: pit-1 and Prop-1, Current Opinion in Endocrinology, Diabetes and Obesity, 15, 359, 10.1097/MED.0b013e3283060a56 Li, 1990, Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1, Nature, 347, 528, 10.1038/347528a0 Pfaffle, 1992, Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia, Science, 257, 1118, 10.1126/science.257.5073.1118 Turton, 2005, Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency, Journal of Clinical Endocrinology and Metabolism, 90, 4762, 10.1210/jc.2005-0570 Gat-Yablonski, 2002, A novel mutation in PIT-1: phenotypic variability in familial combined pituitary hormone deficiencies, Journal of Pediatric Endocrinology and Metabolism, 15, 325, 10.1515/JPEM.2002.15.3.325 de Zegher, 1995, The prenatal role of thyroid hormone evidenced by fetomaternal Pit-1 deficiency, Journal of Clinical Endocrinology and Metabolism, 80, 3127, 10.1210/jc.80.11.3127 Lin, 1994, Pituitary ontogeny of the Snell dwarf mouse reveals Pit-1-independent and Pit-1-dependent origins of the thyrotrope, Development, 120, 515, 10.1242/dev.120.3.515 Salemi, 2003, New N-terminal located mutation (Q4ter) within the POU1F1-gene (PIT-1) causes recessive combined pituitary hormone deficiency and variable phenotype, Growth Hormone and IGF Research, 13, 264, 10.1016/S1096-6374(03)00015-7 Dasen, 1999, Reciprocal interactions of Pit1 and GATA2 mediate signaling gradient-induced determination of pituitary cell types, Cell, 97, 587, 10.1016/S0092-8674(00)80770-9 Sobrier, 2004, Pathophysiology of syndromic combined pituitary hormone deficiency due to a LHX3 defect in light of LHX3 and LHX4 expression during early human development, Gene Expression Patterns, 5, 279, 10.1016/j.modgep.2004.07.003 Sheng, 1996, Specification of pituitary cell lineages by the LIM homeobox gene Lhx3, Science, 272, 1004, 10.1126/science.272.5264.1004 Zhao, 2006, Reduced expression of the LIM-homeobox gene Lhx3 impairs growth and differentiation of Rathke’s pouch and increases cell apoptosis during mouse pituitary development, Mechanism of Development, 123, 605, 10.1016/j.mod.2006.06.005 Mullen, 2007, Roles of the LHX3 and LHX4 LIM-homeodomain factors in pituitary development, Molecular and Cellular Endocrinology, 265–266, 190, 10.1016/j.mce.2006.12.019 Sharma, 1998, LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons, Cell, 95, 817, 10.1016/S0092-8674(00)81704-3 Thaler, 2002, LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein–protein interactions, Cell, 110, 237, 10.1016/S0092-8674(02)00823-1 Rajab, 2008, Novel mutations in LHX3 are associated with hypopituitarism and sensorineural hearing loss, Human Molecular Genetics, 17, 2150, 10.1093/hmg/ddn114 Netchine, 2000, Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency, Nature Genetics, 25, 182, 10.1038/76041 Kristrom, 2009, A novel mutation in the LIM homeobox 3 gene is responsible for combined pituitary hormone deficiency, hearing impairment, and vertebral malformations, Journal of Clinical Endocrinology and Metabolism, 94, 1154, 10.1210/jc.2008-0325 Kelberman, 2009, Genetic regulation of pituitary gland development in human and mouse, Endocrine Reviews, 30, 790, 10.1210/er.2009-0008 Hertzano, 2007, Lhx3, a LIM domain transcription factor, is regulated by Pou4f3 in the auditory but not in the vestibular system, European Journal of Neuroscience, 25, 999, 10.1111/j.1460-9568.2007.05332.x Hume, 2007, Expression of LHX3 and SOX2 during mouse inner ear development, Gene Expression Patterns, 7, 798, 10.1016/j.modgep.2007.05.002 Bhangoo, 2006, Clinical case seminar: a novel LHX3 mutation presenting as combined pituitary hormonal deficiency, Journal of Clinical Endocrinology and Metabolism, 91, 747, 10.1210/jc.2005-2360 Sheng, 1997, Multistep control of pituitary organogenesis, Science, 278, 1809, 10.1126/science.278.5344.1809 Li, 1994, Gsh-4 encodes a LIM-type homeodomain, is expressed in the developing central nervous system and is required for early postnatal survival, EMBO Journal, 13, 2876, 10.1002/j.1460-2075.1994.tb06582.x Raetzman, 2002, Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia, Development, 129, 4229, 10.1242/dev.129.18.4229 Machinis, 2001, Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4, American Journal of Human Genetics, 69, 961, 10.1086/323764 Pfaeffle, 2008, Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies, Journal of Clinical Endocrinology and Metabolism, 93, 1062, 10.1210/jc.2007-1525 Tajima, 2007, A novel missense mutation (P366T) of the LHX4 gene causes severe combined pituitary hormone deficiency with pituitary hypoplasia, ectopic posterior lobe and a poorly developed sella turcica, Journal of Endocrinology, 54, 637 Castinetti, 2008, A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism, Journal of Clinical Endocrinology and Metabolism, 93, 2790, 10.1210/jc.2007-2389 Dateki, 2010, Mutation and gene copy number analyses of six pituitary transcription factor genes in 71 patients with combined pituitary hormone deficiency: identification of a single patient with LHX4 deletion, Journal of Clinical Endocrinology and Metabolism, 95, 4043, 10.1210/jc.2010-0150 Cogan, 1998, The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency, Journal of Clinical Endocrinology and Metabolism, 83, 3346, 10.1210/jc.83.9.3346 Fofanova, 1998, A mutational hot spot in the Prop-1 gene in Russian children with combined pituitary hormone deficiency, Pituitary, 1, 45, 10.1023/A:1009918924945 Lebl, 2005, Auxological and endocrine phenotype in a population-based cohort of patients with PROP1 gene defects, European Journal of Endocrinology, 153, 389, 10.1530/eje.1.01989 Tajima, 2010, A novel mutation (V101A) of the LHX4 gene in a Japanese patient with combined pituitary hormone deficiency, Experimental and Clinical Endocrinology and Diabetes, 118, 405, 10.1055/s-0029-1225612 Okada, 2010, A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci, Human Molecular Genetics, 19, 2303, 10.1093/hmg/ddq091 Guy, 2004, Conserved amino acid sequences confer nuclear localization upon the Prophet of Pit-1 pituitary transcription factor protein, Gene, 336, 263, 10.1016/j.gene.2004.04.022 Lemos, 2006, PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency, Clinical Endocrinology (Oxford), 65, 479, 10.1111/j.1365-2265.2006.02617.x Abrao, 2006, Combined pituitary hormone deficiency (CPHD) due to a complete PROP1 deletion, Clinical Endocrinology (Oxford), 65, 294, 10.1111/j.1365-2265.2006.02592.x Zhang, 2010, A large deletion of PROP1 gene in patients with combined pituitary hormone deficiency from two unrelated Chinese pedigrees, Hormone Research in Paediatrics, 74, 98, 10.1159/000313375 Bertko E, Oostdijk W, Richter-Unruh A, et al. Combined pituitary hormone deficiency (CPHD) in two patients due to gross deletions in PROP1 and POU1F1 (PIT1). 49th Annual ESPE Meeting, Prague; 2010. P1-d1-233. Osorio, 2000, Combined pituitary hormone deficiency caused by a novel mutation of a highly conserved residue (F88S) in the homeodomain of PROP-1, Journal of Clinical Endocrinology and Metabolism, 85, 2779, 10.1210/jc.85.8.2779 Reynaud, 2004, A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies, Journal of Clinical Endocrinology and Metabolism, 89, 5779, 10.1210/jc.2003-032124 Vieira, 2003, Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of Prophet of Pit-1 presenting as constitutional growth delay, Journal of Clinical Endocrinology and Metabolism, 88, 38, 10.1210/jc.2001-011872 Wu, 1998, Mutations in PROP1 cause familial combined pituitary hormone deficiency, Nature Genetics, 18, 147, 10.1038/ng0298-147 Jonsen, 2009, The 26-amino acid beta-motif of the Pit-1beta transcription factor is a dominant and independent repressor domain, Molecular Endocrinology, 23, 1371, 10.1210/me.2008-0137 Okamoto, 1994, Monoallelic expression of normal mRNA in the PIT1 mutation heterozygotes with normal phenotype and biallelic expression in the abnormal phenotype, Human Molecular Genetics, 3, 1565, 10.1093/hmg/3.9.1565 Kishimoto, 2003, The R271W mutant form of Pit-1 does not act as a dominant inhibitor of Pit-1 action to activate the promoters of GH and prolactin genes, European Journal of Endocrinology, 148, 619, 10.1530/eje.0.1480619 Cohen, 1999, Defective retinoic acid regulation of the Pit-1 gene enhancer: a novel mechanism of combined pituitary hormone deficiency, Molecular Endocrinology, 13, 476, 10.1210/me.13.3.476 Miyata, 2006, Identification and functional analysis of the novel S179R POU1F1 mutation associated with combined pituitary hormone deficiency, Journal of Clinical Endocrinology and Metabolism, 91, 4981, 10.1210/jc.2005-2289 Radovick, 1992, A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency, Science, 257, 1115, 10.1126/science.257.5073.1115 Hunter, 2005, LIM-homeodomain genes in mammalian development and human disease, Molecular Biology Reports, 32, 67, 10.1007/s11033-004-7657-z Glenn, 1999, MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene expression, The Journal of Biological Chemistry, 274, 36159, 10.1074/jbc.274.51.36159 Sloop, 2001, An isoform-specific inhibitory domain regulates the LHX3 LIM homeodomain factor holoprotein and the production of a functional alternate translation form, The Journal of Biological Chemistry, 276, 36311, 10.1074/jbc.M103888200 Pfaeffle, 2007, Four novel mutations of the LHX3 gene cause combined pituitary hormone deficiencies with or without limited neck rotation, Journal of Clinical Endocrinology and Metabolism, 92, 1909, 10.1210/jc.2006-2177 Savage, 2007, Mutations in the LHX3 gene cause dysregulation of pituitary and neural target genes that reflect patient phenotypes, Gene, 400, 44, 10.1016/j.gene.2007.05.017 Machinis, 2005, Functional relationship between LHX4 and POU1F1 in light of the LHX4 mutation identified in patients with pituitary defects, Journal of Clinical Endocrinology and Metabolism, 90, 5456, 10.1210/jc.2004-2332 Agarwal, 2000, Adrenocorticotropin deficiency in combined pituitary hormone deficiency patients homozygous for a novel PROP1 deletion, Journal of Clinical Endocrinology and Metabolism, 85, 4556, 10.1210/jc.85.12.4556 Nose, 2006, Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT), Journal of Pediatric Endocrinology and Metabolism, 19, 491 Paracchini, 2003, Two new PROP1 gene mutations responsible for compound pituitary hormone deficiency, Clinical Genetics, 64, 142, 10.1034/j.1399-0004.2003.00106.x Reynaud, 2006, Genetic screening of combined pituitary hormone deficiency: experience in 195 patients, Journal of Clinical Endocrinology and Metabolism, 91, 3329, 10.1210/jc.2005-2173 Tatsumi, 2004, A novel PROP1 gene mutation (157delA) in Japanese siblings with combined anterior pituitary hormone deficiency, Clinical Endocrinology (Oxford), 61, 635, 10.1111/j.1365-2265.2004.02147.x Voutetakis, 2004, Prolonged jaundice and hypothyroidism as the presenting symptoms in a neonate with a novel Prop1 gene mutation (Q83X), European Journal of Endocrinology, 150, 257, 10.1530/eje.0.1500257 Fofanova, 1998, Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency, Journal of Clinical Endocrinology and Metabolism, 83, 2601, 10.1210/jc.83.7.2601 Bircan, 2001, Complete deficiency of growth hormone, thyrotropin and prolactin in two siblings: a new Pit-1 mutation, Journal of Endocrine Genetics, 2, 61 Blankenstein, 2001, A new C-terminal located mutation (V272ter) in the PIT-1 gene manifesting with severe congenital hypothyroidism. Possible functionality of the PIT-1 C-terminus, Hormone Research, 56, 81, 10.1159/000048096 Brown, 1998, Central hypothyroidism reveals compound heterozygous mutations in the Pit-1 gene, Hormone Research, 49, 98, 10.1159/000023134 Carlomagno, 2009, A novel recessive splicing mutation in the POU1F1 gene causing combined pituitary hormone deficiency, Journal of Endocrinological Investigation., 32, 653, 10.1007/BF03345736 Fofanova, 1998, Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency, American Journal of Medical Genetics, 77, 360, 10.1002/(SICI)1096-8628(19980605)77:5<360::AID-AJMG4>3.0.CO;2-R Gat-Yablonski, 2005, Three novel mutations in POU1F1 in Israeli patients with combined pituitary hormone deficiency, Journal of Pediatric Endocrinology and Metabolism, 18, 385, 10.1515/JPEM.2005.18.4.385 Hashimoto, 2003, A novel nonsense mutation in the Pit-1 gene: evidence for a gene dosage effect, Journal of Clinical Endocrinology and Metabolism, 88, 1241, 10.1210/jc.2002-021510 Hendriks-Stegeman, 2001, Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the Pit1/POU1F1 gene, Journal of Clinical Endocrinology and Metabolism, 86, 1545, 10.1210/jc.86.4.1545 Irie, 1995, A novel E250X mutation of the PIT1 gene in a patient with combined pituitary hormone deficiency, Journal of Endocrinology, 42, 351 Malvagia, 2003, The de novo Q167K mutation in the POU1F1 gene leads to combined pituitary hormone deficiency in an Italian patient, Pediatric Research, 54, 635, 10.1203/01.PDR.0000084113.41375.1E McLennan, 2003, Combined pituitary hormone deficiency in Australian children: clinical and genetic correlates, Clinical Endocrinology (Oxford), 58, 785, 10.1046/j.1365-2265.2003.01781.x Ohta, 1992, Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency, Biochemical and Biophysical Research Communications, 189, 851, 10.1016/0006-291X(92)92281-2 Pellegrini-Bouiller, 1996, A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency, Journal of Clinical Endocrinology and Metabolism, 81, 2790, 10.1210/jc.81.8.2790 Pernasetti, 1998, Pro239Ser: a novel recessive mutation of the Pit-1 gene in seven Middle Eastern children with growth hormone, prolactin, and thyrotropin deficiency, Journal of Clinical Endocrinology and Metabolism, 83, 2079, 10.1210/jc.83.6.2079 Rainbow, 2005, Mutation analysis of POUF-1, PROP-1 and HESX-1 show low frequency of mutations in children with sporadic forms of combined pituitary hormone deficiency and septo-optic dysplasia, Clinical Endocrinology (Oxford), 62, 163, 10.1111/j.1365-2265.2004.02189.x Snabboon, 2008, A novel germline mutation, IVS4+1G>A, of the POU1F1 gene underlying combined pituitary hormone deficiency, Hormone Research, 69, 60, 10.1159/000111797 Tatsumi, 1992, Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene, Nature Genetics, 1, 56, 10.1038/ng0492-56