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. 2011 Jan 20:17:218-24.

Lack of KIF21A mutations in congenital fibrosis of the extraocular muscles type I patients from consanguineous Saudi Arabian families

Arif O Khan  1 , Jameela Shinwari, Aisha Omar, Latifa Al-Sharif, Dania S Khalil, Mohammed Alanazi, Abdullah Al-Amri, Nada Al Tassan
Affiliations

Lack of KIF21A mutations in congenital fibrosis of the extraocular muscles type I patients from consanguineous Saudi Arabian families

Arif O Khan et al. Mol Vis. .

Abstract

Purpose: Congenital fibrosis of the extraocular muscles type I (CFEOM1), the most common CFEOM worldwide, is characterized by bilateral ptotic hypotropia, an inability to supraduct above the horizontal midline, horizontal strabismus (typically exotropia), and ophthalmoplegia with abnormal synkinesis. This distinct non-syndromic phenotype is considered autosomal dominant and is virtually always from heterozygous missense mutations in kinesin family member 21A (KIF21A). However, there are occasional KIF21A-negative cases, opening the possibility for a recessive cause. The objective of this study is to explore this possibility by assessing CFEOM1 patients exclusively from consanguineous families, who are the most likely to have recessive cause for their phenotype if a recessive cause exists.

Methods: Ophthalmic examination and candidate gene direct sequencing (KIF21A, paired-like homeobox 2A [PHOX2A], tubulin beta-3 [TUBB3]) of CFEOM1 patients from consanguineous families referred for counseling from 2005 to 2010.

Results: All 5 probands had classic CFEOM1 as defined above. Three had siblings with CFEOM. None of the probands had mutations in KIF21A, PHOX2A, or TUBB3.

Conclusions: The lack of KIF21A mutations in CFEOM1 patients exclusively from consanguineous families, most of whom had siblings with CFEOM, is strong evidence for a recessive form of CFEOM1. Further studies of such families will hopefully uncover the specific locus(loci).

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Figures

Figure 1
Figure 1
Pedigrees for the five CFEOM probands (arrow indicates proband). All individuals indicated as affected were confirmed to be affected to have CFEOM by examination. Question mark indicates that the individual was described as having strabismus but was not available for confirmatory ophthalmic examination.
Figure 2
Figure 2
Typical CFEOM1 phenotype. Patient 1 is shown in forced primary position with his eyelids held upward. He has bilateral blepharoptosis, exotropia, hypotropia, and almost complete ophthalmoloplegia. When released, he assumes a chin up position with a left face turn (because of preference for the right eye).
See this image and copyright information in PMC

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