HESX1 explained

Homeobox expressed in ES cells 1, also known as homeobox protein ANF, is a homeobox protein that in humans is encoded by the HESX1 gene.^[1]

Expression of HEX1 and HESX1 marks the anterior visceral endoderm of the embryo. The AVE is an extra-embryonic tissue, key to the establishment of the anterior-posterior body axis.

Clinical significance

Mutations in the HESX1 gene are associated with some cases of septo-optic dysplasia^[2] or Pickardt-Fahlbusch syndrome.^[3]

Further reading

• Carvalho LR, Brinkmeier ML, Castinetti F, etal . Corepressors TLE1 and TLE3 interact with HESX1 and PROP1. . Mol. Endocrinol. . 24 . 4 . 754–65 . 2010 . 20181723 . 10.1210/me.2008-0359 . 2852357 .
• Kim SS, Kim Y, Shin YL, etal . Clinical characteristics and molecular analysis of PIT1, PROP1,LHX3, and HESX1 in combined pituitary hormone deficiency patients with abnormal pituitary MR imaging . Horm. Res. . 60 . 6 . 277–83 . 2003 . 14646405 . 10.1159/000074245 . 31256955 .
• Torrado M, Revuelta J, Gonzalez C, etal . Role of conserved salt bridges in homeodomain stability and DNA binding . J. Biol. Chem. . 284 . 35 . 23765–79 . 2009 . 19561080 . 10.1074/jbc.M109.012054 . 2749150 . free .
• Dattani MT, Robinson IC . HESX1 and Septo-Optic Dysplasia . Rev Endocr Metab Disord . 3 . 4 . 289–300 . 2002 . 12424431 . 10.1023/A:1020945406356. 26948906 .
• Carvalho LR, Woods KS, Mendonca BB, etal . A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction . J. Clin. Invest. . 112 . 8 . 1192–201 . 2003 . 14561704 . 10.1172/JCI18589 . 213489 .
• Diaczok D, Romero C, Zunich J, etal . A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency . J. Clin. Endocrinol. Metab. . 93 . 11 . 4351–9 . 2008 . 18728160 . 10.1210/jc.2008-1189 . 2582563 .
• Fintini D, Salvatori R, Salemi S, etal . Autosomal-dominant isolated growth hormone deficiency (IGHD type II) with normal GH-1 gene . Horm. Res. . 65 . 2 . 76–82 . 2006 . 16424673 . 10.1159/000091033 . 29894981 .
• Dateki S, Fukami M, Uematsu A, etal . 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 . J. Clin. Endocrinol. Metab. . 95 . 8 . 4043–7 . 2010 . 20534763 . 10.1210/jc.2010-0150 . free .
• Cohen RN, Cohen LE, Botero D, etal . Enhanced repression by HESX1 as a cause of hypopituitarism and septooptic dysplasia . J. Clin. Endocrinol. Metab. . 88 . 10 . 4832–9 . 2003 . 14557462 . 10.1210/jc.2002-021868 . free .
• Sobrier ML, Maghnie M, Vié-Luton MP . Novel HESX1 mutations associated with a life-threatening neonatal phenotype, pituitary aplasia, but normally located posterior pituitary and no optic nerve abnormalities . J. Clin. Endocrinol. Metab. . 91 . 11 . 4528–36 . 2006 . 16940453 . 10.1210/jc.2006-0426 . etal. free .
• Dasen JS, Rosenfeld MG . Signaling and transcriptional mechanisms in pituitary development . Annu. Rev. Neurosci. . 24 . 327–55 . 2001 . 11283314 . 10.1146/annurev.neuro.24.1.327 .
• Tajima T, Hattorri T, Nakajima T, etal . 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. . 88 . 1 . 45–50 . 2003 . 12519827 . 10.1210/jc.2002-020818. free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928.
• Mellado C, Poduri A, Gleason D, etal . Candidate gene sequencing of LHX2, HESX1, and SOX2 in a large schizencephaly cohort . Am. J. Med. Genet. A . 152A . 11 . 2736–42 . 2010 . 20949537 . 10.1002/ajmg.a.33684 . 2965295 .
• Sajedi E, Gaston-Massuet C, Andoniadou CL, etal . DNMT1 interacts with the developmental transcriptional repressor HESX1 . Biochim. Biophys. Acta . 1783 . 1 . 131–43 . 2008 . 17931718 . 10.1016/j.bbamcr.2007.08.010 . 2233781 .
• McNay DE, Turton JP, Kelberman D, etal . HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism . J. Clin. Endocrinol. Metab. . 92 . 2 . 691–7 . 2007 . 17148560 . 10.1210/jc.2006-1609 . free .
• Kelberman D, Dattani MT . Genetics of septo-optic dysplasia . Pituitary . 10 . 4 . 393–407 . 2007 . 17587179 . 10.1007/s11102-007-0055-5 . 25143489 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 10.1073/pnas.242603899 . 139241. 2002PNAS...9916899M . free .
• Ravasi T, Suzuki H, Cannistraci CV, etal . An atlas of combinatorial transcriptional regulation in mouse and man . Cell . 140 . 5 . 744–52 . 2010 . 20211142 . 10.1016/j.cell.2010.01.044 . 2836267 .
• Dattani MT . Borjeson-Forssman-Lehmann syndrome: a novel pituitary phenotype due to mutation in a novel gene . J. Pediatr. Endocrinol. Metab. . 16 . 9 . 1207–9 . 2003 . 14714741 . 10.1515/jpem.2003.16.9.1207. 45542882 .

External links

• GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview

Notes and References

1. Web site: Entrez Gene: HESX homeobox 1.
2. Dattani MT, Martinez-Barbera JP, Thomas PQ, etal . Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse . Nat. Genet. . 19 . 2 . 125–33 . 1998 . 9620767 . 10.1038/477. 28880292 .
3. Reynaud R, Albarel F, Saveanu A, Kaffel N, Castinetti F, Lecomte P, Brauner R, Simonin G, Gaudart J, Carmona E, Enjalbert A, Barlier A, Brue T . Pituitary Stalk Interruption Syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms . Eur J Endocrinol . 164. 4. 457–65. January 2011 . 21270112 . 10.1530/EJE-10-0892 . free .