Screening for PAX6 gene mutations is consistent with haploinsufficiency as the main mechanism leading to various ocular defects

European Journal of Human Genetics

Volumn 11, Issue 2, 2003, Pages 163-169

  Vincent, Marie Claire ^a   Pujo, Anna Laure ^a   Olivier, David ^a   Calvas, Patrick ^a  

^a CHU PURPAN   (France)

Author keywords

Aniridia; Anterior segment dysgenesis; Foveal hypoplasia; PAX6 mutations

Indexed keywords

MESSENGER RNA; TRANSCRIPTION FACTOR PAX6;

ANIRIDIA; ANTERIOR EYE SEGMENT; ARTICLE; CONGENITAL NYSTAGMUS; CONTROLLED STUDY; EYE DEVELOPMENT; EYE MALFORMATION; FAMILIAL DISEASE; FRAMESHIFT MUTATION; GENE CONTROL; GENE DELETION; GENE INSERTION; GENE MUTATION; GENETIC SCREENING; GENETIC VARIABILITY; HUMAN; HYPOPLASIA; MAJOR CLINICAL STUDY; MICROPHTHALMIA; MISSENSE MUTATION; MUTATIONAL ANALYSIS; NONSENSE MUTATION; NUCLEOTIDE SEQUENCE; NULL ALLELE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; RETINA FOVEA; RNA SPLICING; STATISTICAL SIGNIFICANCE; STOP CODON;

EYE ABNORMALITIES; EYE PROTEINS; FEMALE; HETEROZYGOTE; HOMEODOMAIN PROTEINS; HUMANS; MALE; MUTATION; PAIRED BOX TRANSCRIPTION FACTORS; REPRESSOR PROTEINS;

INSERTION SEQUENCES;

EID: 0037300234     PISSN: 10184813     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.ejhg.5200940     Document Type: Article

References (38)

1. Nelson LB, Spaeth GL, Nowinski TS, Margo CE, Jackson LA: A review. Surv Ophthalmol 1984; 28: 621-642.
2. Hanson IM, Fletcher JM, Jordan T et al: Mutations at the Pax6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly. Nature Genet 1994; 6: 168-173.
3. Prosser J, van Heyningen V: Pax6 mutations reviewed. Hum Mutation 1998; 11: 93-108.
4. Chao LY, Huff V, Strong LC, Saunders GF: Mutation in the PAX6 gene in twenty patients with aniridia. Hum Mutation 2000; 15: 332-339.
5. Gessler M, Simola KO, Bruns GA: Cloning of breakpoints of a chromosome translocation identifies the AN2 locus. Science 1989; 244: 1575-1578.
6. Davis LM, Everest AM, Simola KO, Shows TB: Long-range restriction map around 11p13 aniridia locus. Somat Cell Mol Genet 1989; 15: 605-615.
7. Rose EA, Glaser T, Jones C et al: Complete physical map of the WAGR region of 11p13 localizes a candidate Wilms' tumor gene. Cell 1990; 60: 495-508.
8. Lyons LA, Martha A, Mintz-Hittner HA, Saunders GF, Ferrell RE: Resolution of the two loci for autosomal dominant aniridia, AN1 and AN2, to a single locus on chromosome 11p13. Genomics 1992; 13: 925-930.
9. Compton DA, Weil MM, Jones C, Riccardi VM, Strong LC, Saunders GF: Long range physical map of the Wilms' tumor-aniridia region on human chromosome 11. Cell 1988; 55: 827-836.
10. Ton CCT, 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.
11. Glaser T, Walton DS, Maas RL: Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Nature Genet 1992; 2: 232-239.
12. Jordan T, Hanson I, Zaletayev D et al: The human PAX6 gene is mutated in two patients with aniridia. Nature Genet 1992; 1: 328-332.
13. Azuma N, Nishina S, Yanagisawa H, Okuyama T, Yamada M: PAX6 missenses mutation in isolated foveal hypoplasia. Nature Genet 1996; 13: 141-142.
14. Mirzayans F, Pearce WG, MacDonald IM, Walter MA: Mutations of the Pax6 gene in patients with autosomal dominant keratitis. Am J Hum Genet 1995; 57: 539-548.
15. Hodgson SV, Saunders KE: A probable case of the homozygous condition of the aniridia gene. J Med Genet 1980; 6: 478-480.
16. Glaser T, Jepeal L, Edwards JG, Young SR, Favor J, Maas RL: Pax6 gene dosage effect in a family with congenital cataracts, aniridia, anophtalmia and central nervous system defects. Nature Genet 1994; 7: 463-471.
17. Love J, Axton R, Churchill A, van Heyningen V, Hanson I: A new set of primers for mutation analysis of the human Pax6 gene. Hum Mutation 1998; 12: 128-134.
18. Budowle B, Chakraborty R, Guisti A, Eisenberg A, Allen C: Analysis of the VNTR locus D1S80 by the PCR followed by high-resolution PAGE. Am J Hum Genet 1991; 48: 137-144.
19. Sander T, Syagailo Y, Samochowiec J, Okladnova O, Lesh KP, Janz D: Association analysis of a regulatory promoter polymorphism of the PAX6 gene with idiopathic generalized epilepsy. Epilepsy Res 1999; 36: 61-67.
20. Hanson IM, Seawright A, Hardman K: Pax6 mutations in aniridia. Hum Mol Genet 1993; 7: 915-920.
21. Crolla J, Cross I, Atkey N, Wright M, Oley C: FISH studies in a patients with sporadic aniridia and t(7;11)(q31.2;p13). J Med Genet 1996; 33: 66-68.
22. Fantes JA, Bickmore WA, Fletcher JM, Ballesta F, Hanson IM, van Heyningen V: Submicroscopic deletions at the WAGR locus, revealed by nonradioactive in situ hybridization. Am J Hum Genet 1992; 51: 1286-1294.
23. Calvas P, Rozet JM, Gerber S, Munnich A, Kaplan J: Novel PAX6 paired-domain mutations in congenital aniridia and identification of a new alternative splicing of PAX6 mRNA. Am J Hum Genet 1996 (Suppl.59); A394: 2297.
24. Jaworski C, Sperbeck S, Graham C, Wistow G: Alternative splicing of Pax6 in bovine eye and evolutionary conservation of intron sequences. BBR communications 1997; 240: 196-202.
25. Grønskov K, Rosenberg T, Sand A, Brondum Nielsen K: Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype. Eur J Hum Genet 1999; 7: 274-286.
26. 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.
27. Lauderdale J, Wilensky J, Oliver E, Walton E, Walton D, Glaser T: 3′ deletions cause aniridia by preventing PAX6 gene expression. PNAS 2000; 97: 13755-13759.
28. Kondo-Saitoh A, Matsumoto N, Sasaki T et al: Two nonsense mutations of Pax6 in two japanese aniridia families: cases report and review of the literature. Eur J Ophthalmol 2000; 10: 167-172.
29. Gupta S, De Becker I, Guernsey D, Neuman P: Polymerase chain reaction-based risk assessment for Wilms tumor in sporadic aniridia. Am J Ophthalmol 1998; 125: 687-692.
30. Churchill A, Hanson I, Markham A: Prenatal diagnosis of aniridia. Ophthalmology 2000; 107: 1153-1156.
31. Marquat LE, Carmichael GG: Quality control of mRNA function. Cell 2001; 104: 173-176.
32. Byers PH: Killing the messengers: new insights into nonsense-mediated mRNA decay. J Clin Invest 2002; 109: 3-6.
33. Singh S, Tang HK, Lee JY, Saunders G: Truncation mutations in the transactivation region of the PAX6 result in dominant negative mutants. J Biol Chem 1998; 273: 21531-21541.
34. Singh S, Chao L, Mishra R, Davies J, Saunders G: Missense mutation at the C-terminus of PAX6 negatively modulates homeodomain function. Hum Mol Genet 2001; 10: 911-918.
35. Deckwardt S, Neu-Yilik G, Thermann R, Frede U, Hentze MW, Kulozik AE: Abnormally spliced β-globin mRNAs: a single point mutation generates transcripts sensitive and insensitive to nonsense-mediated mRNA decay. Blood 2002; 99: 1811-1816.
36. Hanson IM, Churchill A, Love J et al: Missense mutations in the most ancient residues of the Pax6 paired domain underlie a spectrum of human congenital eye malformation. Hum Mol Genet 1999; 8: 165-172.
37. Sonoda S, Isashiki Y, Tabata Y, Kimura K, Kakiuchi T, Ohba N: A novel Pax6 gene mutation (P118R) in a family with congenital nystagmus associated with a variant form of aniridia. Graefe's Arch Clin Exp Ophthalmol 2000; 238: 552-558.
38. Syagailo Y, Wilke K, Okladnova O et al: Different ocular abnormalities in individuals of a three generation family caused by a new nonsense mutation in the PST domain of the Pax6 gene. Hum. Mutation 1998, on line mutation in brief: 189.