Homozygous mutations in ARIX (PHOX2A) result in congenital fibrosis of the extra ocular muscles type 2. Nakano M, Yamada K, Fain J, Sener EC, Selleck CJ, Awad AH, Zwaan J, Mullaney PB, Bosley TM, Engle EC.∗∗Genetics, The Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 5, Boston, MA, USA. E-mail: engle@enders. tch.harvard.edu Nature Genetics 2001;29:315–320.
2002; Elsevier BV; Volume: 133; Issue: 3 Linguagem: Inglês
10.1016/s0002-9394(02)01367-3
ISSN1879-1891
Autores Tópico(s)Craniofacial Disorders and Treatments
ResumoIsolated strabismus affects 1%–5% of the general population. Most forms of strabismus are multifactorial in origin; although there is probably an inherited component, the genetics of these disorders and even the exact locus of the abnormality resulting in ocular misalignment remain unclear. The congenital fibrosis syndromes (CFS) represent a subset of monogenic isolated strabismic disorders that are characterized by restrictive ophthalmoplegia, and include congenital fibrosis of the extraocular muscles (CFEOM) and Duane syndrome (DURS). Neuropathologic studies indicate that these disorders may result from the maldevelopment of the oculomotor (III), trochlear (IV), and abducens (VI) cranial nerve nuclei. To date, five CFS loci have been mapped (FEOM1, FEOM2, FEOM3, DURS1, and DURS2), but no genes had been identified. In this report, three mutations in ARIX (also know as PHOX2A) were identified in four CFEOM2 pedigrees. ARIX encodes a homeodomain transcription factor protein previously shown to be required for cranial nerves III and IV development in mouse and zebrafish. Two of the mutations are predicted to disrupt splicing, whereas the third alters an amino acid within the conserved brachyury-like domain. These findings confirm the hypothesis that CFEOM2 results from the abnormal development of cranial nerves III and IV and emphasize a critical role for ARIX in the development of these midbrain motor nuclei.—Nancy J. Newman
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