PITX2 and FOXC1 spectrum of mutations in ocular syndromes

European Journal of Human Genetics

Volumn 20, Issue 12, 2012, Pages 1224-1233

  Reis, Linda M ^a   Tyler, Rebecca C ^a   Volkmann Kloss, Bethany A ^a,b   Schilter, Kala F ^a,b   Levin, Alex V ^c   Lowry, R Brian ^d   Zwijnenburg, Petra J G ^e   Stroh, Eliza ^c   Broeckel, Ulrich ^a   Murray, Jeffrey C ^f   Semina, Elena V ^a,b  

^a Children's Research Institute ^*  (United States)

^b MEDICAL COLLEGE OF WISCONSIN   (United States)

^c THOMAS JEFFERSON UNIVERSITY   (United States)

^d UNIVERSITY OF CALGARY   (Canada)

^e VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^f UNIVERSITY OF IOWA   (United States)

Author keywords

anterior segment dysgenesis; Axenfeld Rieger syndrome; De Hauwere syndrome; FOXC1; PITX2

Indexed keywords

TRANSCRIPTION FACTOR FOXC1; TRANSCRIPTION FACTOR PITX2;

ALLELE; CARBOXY TERMINAL SEQUENCE; CHROMOSOME 6P; CONGENITAL HEART MALFORMATION; COPY NUMBER VARIATION; DE HAUWERE SYNDROME; DNA SEQUENCE; FOXF2 GENE; FOXQ1 GENE; GENE; GENE DELETION; GENE MUTATION; GENETIC DISORDER; GENOTYPE; HEARING IMPAIRMENT; HUMAN; MAJOR CLINICAL STUDY; PHENOTYPE; PRIORITY JOURNAL; REVIEW; TOOTH MALFORMATION;

ALLELES; ANTERIOR EYE SEGMENT; BONE AND BONES; DNA COPY NUMBER VARIATIONS; EYE ABNORMALITIES; FACIES; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; GENE DELETION; HEARING LOSS, SENSORINEURAL; HOMEODOMAIN PROTEINS; HUMANS; HYDROCEPHALUS; HYPERTELORISM; JOINT INSTABILITY; MALE; MUSCLE HYPOTONIA; MUTATION; OCULOMOTOR MUSCLES; TRANSCRIPTION FACTORS;

EID: 84869223456     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/ejhg.2012.80     Document Type: Review

References (45)

1. Sowden JC: Molecular and developmental mechanisms of anterior segment dysgenesis. Eye (Lond) 2007; 21: 1310-1318. (Pubitemid 47534744)
2. Reis LM, Semina EV: Genetics of anterior segment dysgenesis disorders. Curr Opin Ophthalmol 2011; 22: 314-324.
3. Rieger H: Verlagerung und schlitzform der pupille mit hypoplasie des irisvorderblattes. Z Augenheilkd 1934; 84: 98-103.
4. Alward WL: Axenfeld-Rieger syndrome in the age of molecular genetics. Am J Ophthalmol 2000; 130: 107-115.
5. Tümer Z, Bach-Holm D: Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. Eur J Hum Genet 2009; 17: 1527-1539.
6. Semina EV, Reiter R, Leysens NJ et al: Cloning and characterization of a novel bicoidrelated homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet 1996; 14: 392-399. (Pubitemid 26414582)
7. Mears AJ, Jordan T, Mirzayans F et al: Mutations of the forkhead/winged-helix gene, FKHL7, in patients with Axenfeld-Rieger anomaly. Am J Hum Genet 1998; 63: 1316-1328. (Pubitemid 30418529)
8. Nishimura DY, Swiderski RE, Alward WL et al: The forkhead transcription factor gene FKHL7 is responsible for glaucoma phenotypes which map to 6p25. Nat Genet 1998; 19: 140-147. (Pubitemid 28248794)
9. Hjalt TA, Semina EV: Current molecular understanding of Axenfeld-Rieger syndrome. Expert Rev Mol Med 2005; 7: 1-17.
10. D'haene B, Meire F, Claerhout I et al: Expanding the spectrum of FOXC1 and PITX2 mutations and copy number changes in patients with anterior segment malformations. Invest Ophthalmol Vis Sci 2011; 52: 324-333.
11. Strungaru MH, Dinu I, Walter MA: Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations. Invest Ophthalmol Vis Sci 2007; 48: 228-237. (Pubitemid 47251407)
12. Kozlowski K, Walter MA: Variation in residual PITX2 activity underlies the phenotypic spectrum of anterior segment developmental disorders. Hum Mol Genet 2000; 9: 2131-2139.
13. Espinoza HM, Cox CJ, Semina EV, Amendt BA: A molecular basis for differential developmental anomalies in Axenfeld-Rieger syndrome. Hum Mol Genet 2002; 11: 743-753. (Pubitemid 34428642)
14. Maciolek NL, Alward WL, Murray JC, Semina EV, McNally MT: Analysis of RNA splicing defects in PITX2 mutants supports a gene dosage model of Axenfeld-Rieger syndrome. BMC Med Genet 2006; 7: 59.
15. Priston M, Kozlowski K, Gill D et al: Functional analyses of two newly identified PITX2 mutants reveal a novel molecular mechanism for Axenfeld-Rieger syndrome. Hum Mol Genet 2001; 10: 1631-1638. (Pubitemid 32776292)
16. Saadi I, Semina EV, Amendt BA et al: Identification of a dominant negative homeodomain mutation in Rieger syndrome. J Biol Chem2001; 276: 23034-23041.
17. Saadi I, Toro R, Kuburas A, Semina E, Murray JC, Russo AF: An unusual class of PITX2 mutations in Axenfeld-Rieger syndrome. Birth Defects Res A Clin Mol Teratol 2006; 76: 175-181.
18. Lines MA, Kozlowski K, Kulak SC et al: Characterization and prevalence of PITX2 microdeletions and mutations in Axenfeld-Rieger malformations. Invest Ophthalmol Vis Sci 2004; 45: 828-833. (Pubitemid 38868378)
19. Volkmann BA, Zinkevich NS, Mustonen A et al: Potential novel mechanism for axenfeld-rieger syndrome: deletion of a distant region containing regulatory elements of PITX2. Invest Ophthalmol Vis Sci 2011; 52: 1450-1459.
20. Lehmann OJ, Ebenezer ND, Ekong R et al: Ocular developmental abnormalities and glaucoma associated with interstitial 6p25 duplications and deletions. Invest Ophthalmol Vis Sci 2002; 43: 1843-1849. (Pubitemid 34587030)
21. De Hauwere RC, Leroy JG, Adriaenssens K, Van Heule R: Iris dysplasia, orbital hypertelorism, and psychomotor retardation: a dominantly inherited developmental syndrome. J Pediatr 1973; 82: 679-681.
22. Lowry RB, Gould DB, Walter MA, Savage PR: Absence of PITX2, BARX1, and FOXC1 mutations in De Hauwere syndrome (Axenfeld-Rieger anomaly, hydrocephaly, hearing loss): a 25-year follow up. Am J Med Genet A 2007; 143A: 1227-1230. (Pubitemid 46870080)
23. Bremond-Gignac D, Bitoun P, Reis LM, Copin H, Murray JC, Semina EV: Identification of dominant FOXE3 and PAX6 mutations in patients with congenital cataract and aniridia. Mol Vis 2010; 16: 1705-1711.
24. Kaur K, Ragge NK, Ragoussis J: Molecular analysis of FOXC1 in subjects presenting with severe developmental eye anomalies. Mol.Vis 2009; 15: 1366-1373.
25. Exome Variant Server: NHLBI Exome Sequencing Project (ESP). Seattle, WA, November 2011.
26. Reis LM, Tyler RC, Schilter KF et al: BMP4 loss-of-function mutations in developmental eye disorders including SHORT syndrome. Hum Genet 2011; 130: 495-504.
27. Divina P, Kvitkovicova A, Buratti E, Vorechovsky I: Ab initio prediction of mutation-induced cryptic splice-site activation and exon skipping. Eur J Hum Genet 2009; 17: 759-765.
28. Nagy E, Maquat LE: A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. Trends Biochem Sci 1998; 23: 198-199. (Pubitemid 28302613)
29. Karadeniz NN, Kocak-Midillioglu I, Erdogan D, Bokesoy I: Is SHORT syndrome another phenotypic variation of PITX2? Am J Med Genet A 2004; 130A: 406-409. (Pubitemid 39441620)
30. Lauderdale JD, Wilensky JS, Oliver ER, Walton DS, Glaser T: 3' deletions cause aniridia by preventing PAX6 gene expression. Proc Natl Acad Sci USA 2000; 97: 13755-13759.
31. Borges AS, Susanna Jr R, Carani JC et al: Genetic analysis of PITX2 and FOXC1 in Rieger Syndrome patients from Brazil. J Glaucoma 2002; 11: 51-56. (Pubitemid 34131081)
32. Gould DB, Jaafar MS, Addison MK et al: Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: relevance to ocular dysgenesis and hearing impairment. BMC Med Genet 2004; 5: 17.
33. DeScipio C: The 6p subtelomere deletion syndrome. Am J Med Genet C Semin Med Genet 2007; 145C: 377-382.
34. Mirza G, Williams RR, Mohammed S et al: Refined genotype-phenotype correlations in cases of chromosome 6p deletion syndromes. Eur J Hum Genet 2004; 12: 718-728. (Pubitemid 39264055)
35. Maclean K, Smith St J, Heaps L et al: Axenfeld-Rieger malformation and distinctive facial features: clues to a recognizable 6p25 microdeletion syndrome. Am J Med Genet A 2005; 132: 381-385. (Pubitemid 40175588)
36. Kannu P, Oei P, Slater HR, Khammy O, Aftimos S: Epiphyseal dysplasia and other skeletal anomalies in a patient with the 6p25 microdeletion syndrome. Am J Med Genet A 2006; 140: 1955-1959. (Pubitemid 44380085)
37. Martinez-Glez V, Lorda-Sanchez I, Ramirez JM et al: Clinical presentation of a variant of Axenfeld-Rieger syndrome associated with subtelomeric 6p deletion. Eur J Med Genet 2007; 50: 120-127. (Pubitemid 46401577)
38. Bedoyan JK, Lesperance MM, Ackley T, Iyer RK, Innis JW, Misra VK: A complex 6p25 rearrangement in a child with multiple epiphyseal dysplasia. Am J Med Genet A 2011; 155A: 154-163.
39. Anderlid BM, Schoumans J, Hallqvist A et al: Cryptic subtelomeric 6p deletion in a girl with congenital malformations and severe language impairment. Eur J Hum Genet 2003; 11: 89-92. (Pubitemid 36175790)
40. Hong HK, Lass JH, Chakravarti A: Pleiotropic skeletal and ocular phenotypes of the mouse mutation congenital hydrocephalus (ch/Mf1) arise from a winged helix/forkhead transcriptionfactor gene. Hum Mol Genet 1999; 8: 625-637. (Pubitemid 29139977)
41. Kume T, Deng KY, Winfrey V, Gould DB, Walter MA, Hogan BL: The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation congenital hydrocephalus. Cell 1998; 93: 985-996. (Pubitemid 28280792)
42. Wang T, Tamakoshi T, Uezato T et al: Forkhead transcription factor Foxf2 (LUN)-deficient mice exhibit abnormal development of secondary palate. Dev Biol 2003; 259: 83-94. (Pubitemid 36703145)
43. McKeone R, Vieira H, Gregory-Evans K, Gregory-Evans CY, Denny P: Foxf2: a novel locus for anterior segment dysgenesis adjacent to the foxc1 gene. PLoS One 2011; 6: e25489.
44. Hong HK, Noveroske JK, Headon DJ et al: The winged helix/forkhead transcription factor Foxq1 regulates differentiation of hair in satin mice. Genesis 2001; 29: 163-171. (Pubitemid 32417239)
45. Planchart A, Mattingly CJ: 2,3,7,8-Tetrachlorodibenzo-p-dioxin upregulates FoxQ1b in zebrafish jaw primordium. Chem Res Toxicol 2010; 23: 480-487.