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. 1999 Dec;65(6):1639-46.
doi: 10.1086/302656.

Localization of a gene for Duane retraction syndrome to chromosome 2q31

B Appukuttan  1 , E Gillanders, S H Juo, D Freas-Lutz, S Ott, R Sood, A Van Auken, J Bailey-Wilson, X Wang, R J Patel, C M Robbins, M Chung, G Annett, K Weinberg, M S Borchert, J M Trent, M J Brownstein, J T Stout
Affiliations

Localization of a gene for Duane retraction syndrome to chromosome 2q31

B Appukuttan et al. Am J Hum Genet. 1999 Dec.

Abstract

Duane retraction syndrome (DRS) is a congenital eye-movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting in restriction or absence of abduction, restricted adduction, and narrowing of the palpebral fissure and retraction of the globe on attempted adduction. DRS has a prevalence of approximately 0.1% in the general population and accounts for 5% of all strabismus cases. Undiagnosed DRS in children can lead to amblyopia, a permanent uncorrectable loss of vision. A large family with autosomal dominant DRS was examined and tested for genetic linkage. After exclusion of candidate regions previously associated with DRS, a genomewide search with highly polymorphic microsatellite markers was performed, and significant evidence for linkage was obtained at chromosome 2q31 (D2S2314 maximum LOD score 11.73 at maximum recombination fraction. 0). Haplotype analysis places the affected gene in a 17.8-cM region between the markers D2S2330 and D2S364. No recombinants were seen with markers between these two loci. The linked region contains the homeobox D gene cluster. Three of the genes within this cluster, known to participate in hindbrain development, were sequenced in affected and control individuals. Coding sequences for these genes were normal or had genetic alterations unlikely to be responsible for the DRS phenotype. Identifying the gene responsible for DRS may lead to an improved understanding of early cranial-nerve development.

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Figures

Figure 1
Figure 1
Photodocumentation of a patient with DRS, exhibiting incomplete abduction on attempted right or left gaze.
Figure 2
Figure 2
Pedigree of the large DRS family used for linkage analysis. All individuals, with the exception of the deceased and individuals (denoted by a minus sign [−]), were examined for DRS. DNA was prepared from subjects and was genotyped for linkage analysis. Individuals denoted with a plus sign (+) were used to confine the critical disease region (see fig. 5). Individual III-16 was phenotypically classified as “indeterminate.”
Figure 3
Figure 3
Graph of multipoint LOD scores, between DRS and chromosome 2 markers D2S142, D2S333, D2S335, D2S1238, D2S2314, D2S1244, D2S1245, HOXD13, and D2S138, for the large Mexican family.
Figure 4
Figure 4
Schematic representation of the genetic map of the region containing the DRS locus. The flanking proximal and distal markers, separated by 17.8 cM, are shown in boldface. The distances (in cM) between the markers D2S160, D2S112, D2S142, D2S2330, D2S333, D2S364, D2S117, D2S382, and D2S396 are underlined. The order of and the genetic distances between markers were obtained from the PE Biosystems ABI PRISM mapping Web page.
Figure 5
Figure 5
Haplotypes for chromosome 2 markers, for a subset of the large Mexican family with DRS. The order of the DNA markers is shown. The disease-associated alleles are boxed. The critical interval lies between markers D2S2330 and D2S364 and is indicated by the arrows. Two other markers, D2S335 and D2S1244 (not shown), are also within this critical interval.
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References

Electronic-Database Information

    1. GenBank, http://www.ncbi.nlm.nih.gov/GenBank (for gene locations)
    1. Genetic Location Database, http://cedar.genetics.soton.ac.uk/ (for markers used for haplotype analysis)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/omim (for Duane retraction syndrome [MIM 126800])
    1. PE Biosystems, http://www.pebio.com/ab/apply/dr/dra1a3.html (for markers used for linkage analysis), http://www2.perkin-elmer.com/ab/apply/dr/lmsv2/chrom2.html (for ABI PRISM mapping)

References

    1. Bedford M, Arman E, Orr-Urtreger A, Lonai P (1995) Analysis of the Hoxd-3 gene: structure and localization of its sense and natural antisense transcripts. DNA Cell Biol 14(4): 295–304 - PubMed
    1. Calabrese GSL, Morizio E, Franchi PG, Pompetti F, Mingarelli R, Marsilio T, Rocchi M, et al (1998) Detection of an insertion deletion of region 8q13-q21.2 in a patient with Duane syndrome: implications for mapping and cloning a Duane gene. Eur J Hum Genet 6(3): 187–193 - PubMed
    1. Carpenter EM, Goddard JM, Chisaka O, Manley NR, Capecchi MR (1993) Loss of Hox-A1 (Hox-1.6) function results in the reorganization of the murine hindbrain. Development 118:1063–1075 - PubMed
    1. Chew CK, Foster P, Hurst JA, Salmon JF (1995) Duane's retraction syndrome associated with chromosome 4q27-31 segment deletion. Am J Ophthalmol 119(6): 807–809 - PubMed
    1. Chung M, Stout JT, Borchert MS. Clinical diversity of hereditary duane's retraction syndrome. Ophthalmology (in press) - PubMed

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