Confirmation of RAX gene involvement in human anophthalmia.
Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. Mutations in several genes have been involved in syndromic and non-syndromic anophthalmia. Previously, RAX recessive mutations were implicated in a single patient with right anophthalmia, left microphthalmia and sclerocornea. In this study, we report the findings of novel compound heterozygous RAX mutations in a child with bilateral anophthalmia. Both mutations are located in exon 3. c.664delT is a frameshifting deletion predicted to introduce a premature stop codon (p.Ser222ArgfsX62), and c.909C>G is a nonsense mutation with similar consequences (p.Tyr303X). This is the second report of a patient with anophthalmia caused by RAX mutations. These findings confirm that RAX plays a major role in the early stages of eye development and is involved in human anophthalmia.
Lequeux
L
L
INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
Rio
M
M
Vigouroux
A
A
Titeux
M
M
Etchevers
H
H
Malecaze
F
F
Chassaing
N
N
Calvas
P
P
D000853:Anophthalmos / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D003315:Cornea / Q000002:abnormalities; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009915:Orbit / Q000002:abnormalities; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*
D005136:Eye Proteins; D018398:Homeodomain Proteins; C486393:RAX protein, human; D014157:Transcription Factors
Dev Biol. 2000 Jul 15;223(2):422-30
10882526
Genesis. 2001 Sep;31(1):43-53
11668677
Orphanet J Rare Dis. 2007 Nov 26;2:47
18039390
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2343-8
9482887
Int J Dev Biol. 2004;48(8-9):761-70
15558469
Am J Hum Genet. 2008 Feb;82(2):304-19
18252212
Development. 1999 Jun;126(11):2451-60
10226004
Nature. 1997 Jun 5;387(6633):603-7
9177348
J Med Genet. 2002 Jan;39(1):16-22
11826019
Nat Genet. 2003 Apr;33(4):461-3
12612584
Genesis. 2000 Nov-Dec;28(3-4):135-42
11105055
Can J Ophthalmol. 2005 Feb;40(1):38-44
15825528
Dev Biol. 2004 May 15;269(2):567-79
15110720
EMBO Rep. 2003 Sep;4(9):894-9
12947416
DNA Cell Biol. 2001 Feb;20(2):89-99
11244566
Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3088-93
9096350
Mol Cell Biol. 1999 Oct;19(10):7001-10
10490637
Nat Genet. 1998 Jun;19(2):125-33
9620767
Development. 2003 Nov;130(21):5143-54
12975341
Hum Mol Genet. 2004 Feb 1;13(3):315-22
14662654
Hum Genet. 2005 Nov;118(2):214-24
16133182
Am J Med Genet A. 2005 May 15;135(1):1-7; discussion 8
15812812