Lack of KIF21A mutations in congenital fibrosis of the extraocular muscles type I patients from consanguineous Saudi Arabian families.
OBJECTIVE
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).
Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. arif.khan@mssm.edu
Arif O
AO
Khan
Jameela
J
Shinwari
Aisha
A
Omar
Latifa
L
Al-Sharif
Dania S
DS
Khalil
Mohammed
M
Alanazi
Abdullah
A
Al-Amri
Nada
N
Al Tassan
D000293:Adolescent; D001763:Blepharoptosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D017931:DNA Primers / Q000235:genetics; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009801:Oculomotor Muscles / Q000473:pathology*; D009886:Ophthalmoplegia / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D012529:Saudi Arabia
D017931:DNA Primers; C119023:KIF21A protein, human; D016547:Kinesins
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