A novel PHOX2A/ARIX mutation in an iranian family with congenital fibrosis of extraocular muscles type 2 (CFEOM2)

Yazdani, Ahmad; Chung, Daniel C.; Abbaszadegan, Mohammad Reza; Al-Khayer, Kholoud; Chan, Wai Man; Yazdani, Milad; Ghodsi, Kazem; Engle, Elizabeth C.; Traboulsi, Elias I.

doi:10.1016/s0002-9394(03)00891-2

Cited by 39 publications

(16 citation statements)

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“…We initially identified three distinct mutations, two predicted to disrupt splicing and one that alters an amino acid within the conserved brachyurylike domain (27). Subsequently, collaborative work led to the identification of a homozygous nonsense mutation in the coding region of PHOX2A in an Iranian pedigree with CFEOM2 (28). This nonsense mutation provided strong evidence that the human CFEOM2 phenotype results from a complete loss of function of PHOX2A.…”

Section: Cfeom2mentioning

confidence: 99%

The Genetic Basis of Complex Strabismus

Engle

2006

Pediatr Res

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Members of my research laboratory combine clinical, genetic, and molecular biologic approaches to the study of congenital strabismus. Strabismus, which is misalignment of the eyes, affects 2-4% of the population and causes loss of binocular vision and amblyopia (vision loss in a structurally normal eye). The cause of strabismus when it occurs in the absence of structural brain abnormalities is generally unknown. In the last decade, we have focused our research studies on understanding the genetic etiology of a series of complex strabismus syndromes in which eye movement in at least one direction is limited or paralyzed. We are discovering that these disorders result from mutations in genes necessary for the normal development and connectivity of brainstem ocular motoneurons, including PHOX2A, SALL4, KIF21A, ROBO3, and HOXA1, and we now refer to these syndromes as the "congenital cranial dysinnervation disorders," or CCDD. (Pediatr Res 59: 343-348, 2006)

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Section: Cfeom2mentioning

confidence: 99%

The Genetic Basis of Complex Strabismus

Engle

2006

Pediatr Res

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“…We have identified this recessive disorder in consanguineous pedigrees, mapped it to the FEOM2 locus on 11q13, 9 and shown that it results from homozygous mutations in PHOX2A (ARIX). 10,11 PHOX2A encodes a homeodomain transcription factor essential to the development of the oculomotor and trochlear motoneurons in mice and zebrafish. 12,13 Hence, we propose that these cranial nuclei fail to form in CFEOM2 probands.…”

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confidence: 99%

Identification ofKIF21AMutations as a Rare Cause of Congenital Fibrosis of the Extraocular Muscles Type 3 (CFEOM3)

Yamada

Chan

Andrews

et al. 2004

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.Three congenital fibrosis of the extraocular muscles phenotypes (CFEOM1-3) have been identified. Each represents a specific form of paralytic strabismus characterized by congenital restrictive ophthalmoplegia, often with accompanying ptosis. It has been demonstrated that CFEOM1 results from mutations in KIF21A and CFEOM2 from mutations in PHOX2A. This study was conducted to determine the incidence of KIF21A and PHOX2A mutations among individuals with the third CFEOM phenotype, CFEOM3. METHODS. All pedigrees and sporadic individuals with CFEOM3 in the authors' database were identified, whether the pedigrees were linked or consistent with linkage to the FEOM1, FEOM2, and/or FEOM3 loci was determined, and the appropriate pedigrees and the sporadic individuals were screened for mutations in KIF21A and PHOX2A. RESULTS. Twelve CFEOM3 pedigrees and 10 CFEOM3 sporadic individuals were identified in the database. The structures of eight of the pedigrees permitted the generation of meaningful linkage data. KIF21A was screened in 17 probands, and mutations were identified in two CFEOM3 pedigrees. One pedigree harbored a novel mutation (2841G3 A, M947I) and one harbored the most common and recurrent of the CFEOM1 mutations identified previously (2860C3 T, R954W). None of CFEOM3 pedigrees or sporadic individuals harbored mutations in PHOX2A.CONCLUSIONS. The results demonstrate that KIF21A mutations are a rare cause of CFEOM3 and that KIF21A mutations can be nonpenetrant. Although KIF21A is the first gene to be associated with CFEOM3, the results imply that mutations in the unidentified FEOM3 gene are the more common cause of this phenotype. (Invest Ophthalmol Vis Sci.

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“…13 The ARIX gene mutations have been detected only in families from Middle Eastern countries, such as Saudi Arabia, Turkey, and Iran. 13,14 In families with CFEOM1 and CFEOM3, the disease is inherited in an autosomal dominant fashion. In most autosomal dominant CFEOM families reported so far, the disease has been mapped to the CFEOM1 locus, 4-7,15,16 while in only two CFEOM families has it been mapped to the CFEOM3 locus.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Mutation of the KIF21A Gene in Japanese Patients with Congenital Fibrosis of the Extraocular Muscles

2005

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The KIF21A gene mutation R954W was detected in the patients with CFEOM1 screened in this study, all of whom were Japanese, reflecting similar reports from Europe, America, the Middle East, and Japan. We suggest that mutations of the KIF21A gene contribute to the development of CFEOM1 regardless of ethnicity. We also found that the delimitation of the KIF21A gene mutation site enabled us to efficiently detect the KIF21A gene mutation despite the large number of KIF21A gene exons.

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A novel PHOX2A/ARIX mutation in an iranian family with congenital fibrosis of extraocular muscles type 2 (CFEOM2)

Cited by 39 publications

References 13 publications

The Genetic Basis of Complex Strabismus

The Genetic Basis of Complex Strabismus

Identification ofKIF21AMutations as a Rare Cause of Congenital Fibrosis of the Extraocular Muscles Type 3 (CFEOM3)

Recurrent Mutation of the KIF21A Gene in Japanese Patients with Congenital Fibrosis of the Extraocular Muscles

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