Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype

European Journal of Human Genetics

Volumn 7, Issue 3, 1999, Pages 274-286

  Grønskov, Karen ^a   Rosenberg, Thomas ^b   Sand, Annie ^a   Brøndum Nielsen, Karen ^a  

^a JOHN F KENNEDY INSTITUTE   (Denmark)

^b National Eye Clinic for the Visually Impaired Denmark   (Denmark)

Author keywords

Alternative splicing; Aniridia; Missense mutations; PAX6; Phenotype genotype correlation

Indexed keywords

DNA;

ALTERNATIVE RNA SPLICING; ANIRIDIA; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DENMARK; DNA FINGERPRINTING; GENE DOSAGE; GENE MUTATION; HUMAN; HUMAN CELL; MISSENSE MUTATION; PHENOTYPE; PRIORITY JOURNAL;

EID: 0032903663     PISSN: 10184813     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.ejhg.5200308     Document Type: Article

References (54)

1. Hanson I, van Heyningen V: PAX6: more than meets the eye. Trends Genet 1995; 11: 268-272.
2. van Heyningen V, Hastie ND: Wilms' tumour: reconciling genetics and biology. Trends Genet 1992; 8: 16-21.
3. Ton CC, Hirvonen H, Miwa H et al: Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell 1991; 67: 1059-1074.
4. Walther C, Gruss P: Pax-6, a murine paired box gene, is expressed in the developing CNS. Development 1991; 113: 1435-1449.
5. Ton CC, Miwa H, Saunders GF: Small eye (Sey): cloning and characterization of the murine homolog of the human aniridia gene. Genomics 1992; 13; 251-256.
6. Martin P, Carriere C, Dozier C et al: Characterization of a paired box- and homeobox-containing quail gene (Pax-QNR) expressed in the neuroretina. Oncogene 1992; 7: 1721-1728.
7. Matsuo T, Osumi Yamashita N, Noji S et al: A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells. Nat Genet 1993; 3: 299-304.
8. Li HS, Yang JM, Jacobson RD, Pasko D, Sundin O: Pax-6 is first expressed in a region of ectoderm anterior to the early neural plate: implications for stepwise determination of the lens. Dev Biol 1994; 162: 181-194.
9. Krauss S, Johansen T, Korzh V, Moens U, Ericson JU, Fjose A: Zebrafish pax[zf-a]: a paired box-containing gene expressed in the neural tube. EMBO J 1991; 10: 3609-3619.
10. Puschel AW, Gruss P, Westerfield M: Sequence and expression pattern pax-6 are highly conserved between zebrafish and mice. Development 1992; 114: 643-651.
11. Quiring R, Walldorf U, Kloter U, Gehring WJ: Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans [see comments]. Science 1994; 265: 785-789.
12. Czerny T, Busslinger M: DNA-binding and transactivation properties of Pax-6: three amino acids in the paired domain are responsible for the different sequence recognition of Pax-6 and BSAP (Pax-5). Mol Cell Biol 1995; 15: 2858-2871.
13. Chisholm AD, Horvitz HR: Patterning of the Caenorhabditis elegans head region by the Pax-6 family member vab-3. Nature 1995; 377: 52-55.
14. Zhang Y, Emmons SW: Specification of sense-organ identity by a Caenorhabditis elegans Pax-6 homologue. Nature 1995; 377: 55-59.
15. Loosli F, Kmita Cunisse M, Gehring WJ: Isolation of a Pax-6 homolog from the ribbonworm Lineus sanguineus. Proc Natl Acad Sci USA 1996; 93: 2658-2663.
16. Glardon S, Callaerts P, Halder G, Gehring WJ: Conservation of Pax-6 in a lower chordate, the ascidian Phallusia mammillata. Development 1997; 124: 817-825.
17. Hirsch N, Harris WA: Xenopus Pax-6 and retinal development. J Neurobiol 1997; 32: 45-61.
18. Glaser T, Walton DS, Maas RL: Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Nat Genet 1992; 2: 232-239.
19. Epstein JA, Glaser T, Cai J, Jepeal L, Walton DS, Maas RL: Two independent and interactive DNA-binding sub-domains of the PAX6 paired domain are regulated by alternative splicing. Genes Dev 1994: 8: 2022-2034.
20. Jaworski C, Sperbeck S, Graham C, Wistow G: Alternative splicing of PAX6 in bovine eye and evolutionary conservation of intron sequences. Biochem Biophys Res Comm 1997; 240: 196-202.
21. Carriere C, Plaza S, Martin P et al: Characterization of quail Pax-6 (Pax-QNR) proteins expressed in the neuroretina. Mol Cell Biol 1993; 13: 7257-7266.
22. Mermod N, O'Neill EA, Kelly TJ, Tijan R: The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell 1989; 58: 741-753.
23. Tanaka M, Herr W: Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation. Cell 1990; 60: 375-386.
24. Glaser T, Jepeal L, Edwards JG, Young SR, Favor J, Maas RL: PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects [published erratum appears in Nat Genet 1994 Oct; 8(2): 203]. Nat Genet 1994; 7: 463-471.
25. Tang HK, Singh S, Saunders G: Dissection of the transactivation function of the transcription factor encoded by the eye development gene PAX6. J Biol Chem 1998; 273: 7210-7221.
26. Plaza S, Dozier C, Saule S: Quail Pax-6 (Pax-QNR) encodes a transcription factor able to bind and transactivate its own promoter. Cell Growth Differ 1993; 4: 1041-1050.
27. Callaerts P, Halder G, Gehring WJ: PAX-6 in development and evolution. Annu Rev Neurosci 1997; 20:00-00
28. Wehr R, Gruss P: Pax and vertebrate development. Int J Dev Biol 1996; 40: 369-377.
29. Bopp D, Burri M, Baumgartner S, Frigerio G, Noll M: Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila. Cell 1986; 47: 1033-1040.
30. Hill RE, Favor J, Hogan BL et al: Mouse small eye results from mutations in a paired-like homeobox-containing gene [published erratum appears in Nature 1992 Feb 20; 355(6362):750]. Nature 1991; 354: 522-525.
31. Brown A, McKie M, van Heyningen V, Prosser J: The human PAX6 mutation database. Nucleic Acids Res 1998; 26: 259-264.
32. Prosser J, van Heyningen V: PAX6 mutations reviewed. Hum Mutat 1998; 11: 93-108.
33. Hanson IM, Seawright A, Hardman K et al: PAX6 mutations in aniridia. Hum Mol Genet 1993; 2: 915-920.
34. Tang HK, Chao LY, Saunders GF: Functional analysis of paired box missense mutations in the PAX6 gene. Hum Mol Genet 1997; 6: 381-386.
35. Hanson IM, Fletcher JM, Jordan T et al: Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly. Nat Genet 1994; 6: 168-173.
36. Azuma N. Nishina S, Yanagisawa H, Okuyama T, Yamada M: PAX6 missense mutation in isolated foveal hypoplasia. Nat Genet 1996; 13: 141-142.
37. Azuma N, Yamada M: Missense mutation at the C terminus of the PAX6 gene in ocular anterior segment anomalies. Invest Ophthalmol Vis Sci 1998; 39: 828-830.
38. Mirzayans F, Pearce WG, MacDonald IM, Walter MA: Mutation of the PAX6 gene in patients with autosomal dominant keratitis. Am J Hum Genet 1995; 57: 539-548.
39. Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
40. Maas RL, Epstein JA, Glaser T: Identification and functional analysis of mutations in the human PAX6 gene. Methods Mol Genet 1996; 8: 40-69.
41. Sarkar G, Sup H-S. Sommer SS: Dideoxy fingerprinting (ddF): A rapid and efficient screen for the presence of mutations. Genomics 1992; 13: 441-443.
42. Axton R, Hanson I, Danes S, Sellar G, van Heyningen V, Prosser J: The incidence of PAX6 mutation in patients with simple aniridia: an evaluation of mutation detection in 12 cases. J Med Genet 1997; 34: 279-286.
43. Xu W, Rould MA, Jun S, Desplan C, Pabo CO: Crystal structure of a paired domain-DNA complex at 2.5 A resolution reveals structural basis for Pax developmental mutations. Cell 1995; 80: 639-650.
44. Davis A, Cowell JK: Mutations in the PAX6 gene in patients with hereditary aniridia. Hum Mol Genet 1993; 2: 2093-2097.
45. Churchill AJ, Anwar R, Markham AF: PAX6, aniridia and Peters' anomaly. [Abstract] Invest Ophtalmol Vis Sci 1997; 38: (4) 112-123.
46. Halder G, Callaerts P, Gehring WJ: Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila [see comments]. Science 1995; 267: 1788-1792.
47. Fantes J, Redeker B, Breen M et al: Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype. Hum Mol Genet 1995; 4: 415-422.
48. Eiken HG, Knappskog PM, Apold J, Skjelkvåle L, Boman H: A de novo phenylketonuria mutation: ATG (Met) to ATA (Ile) in the start codon of the phenylalanine hydroxylase gene. Hum Mutat 1992; 1: 388-391.
49. Saba L, Meloni A, Sardu R et al: A novel b-thalassemia mutation (G-A) at the initiation codon of the b-globin gene. Hum Mutat 1992; 1: 420-422.
50. Sistermans EA, de Wijs IJ, de Coo RFM, Smit LME, Menko FH, van Oost BA: A (G-to-A) mutation in the initiation codon of the proteolipid protein gene causing a relatively mild form of Pelizaeus-Merzbacher disease in a Dutch family. Hum Genet 1996; 97: 337-339.
51. Inoue H, Nomiyama J, Nakai K, Matsutani A, Tanisawa Y, Oka Y: Isolation of full-length cDNA of mouse PAX4 gene and identification of its human homologue. Biochem Biophys Res Comm 1998; 243: 628-633.
52. Glaser T, Walton DS, Cai J et al: PAX6 gene mutations in Aniridia. In: Wiggs JL (ed.). Molecular Genetics of Ocular Disease. Wiley-Liss: New York, 1995, vol 3, pp 51-82.
53. Carriere C, Plaza S. Caboche J et al: Nuclear localization signals, DNA binding, and transactivation properties of quail Pax-6 (Pax-QNR) isoforms. Cell Growth Differ 1995; 6: 1531-1540.
54. Martha A, Ferrell RE, Mintz Hittner H, Lyons LA, Saunders GF: Paired box mutations in familial and sporadic aniridia predicts truncated aniridia proteins [published erratum appears in Am J Hum Genet 1994 Sep; 55(3):602]. Am J Hum Genet 1994; 54: 801-811.