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E.C. Engle, C. Andrews, K. Law, W.–M. Chan, J.L. Demer; Clinical And Genetic Analysis Of Two Duane Syndrome Pedigrees That Map To The Durs2 Locus . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4575.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Duane syndrome (DS) is the most common of the congenital cranial dysinnervation syndromes, and the genetic basis of isolated DS is not yet known. Only one isolated DS locus has been defined by linkage analysis of DS pedigrees. This locus, DURS2, was mapped by Appukuttan et al in 1999 based on the results of a genome–wide screen for linkage in a large Mexican DS pedigree. The 17.8–cM DURS2 region on chromosome 2q31 was then refined to an 8.8–cM region in an English DS pedigree by Evans et al in 2000. The purpose of this study is to define the clinical characteristics of two additional dominant DS pedigrees, FY and JH, and to determine if their phenotypes also map to the DURS2 locus. Methods: A subset of family members underwent clinical examinations to define their DS phenotype. Blood samples were obtained from participating family members and DNA was extracted using standard methods. Each pedigree was analyzed for linkage to the DURS2 region by PCR amplification of a subset of polymorphic markers including D2S142, D2S2300, D2S335, D2S326, D2S2314, D2S364 and D2S117. Lod scores were calculated using MLINK and assuming a disease allele frequency of 0.00001 and a penetrance of 95%. Results: Pedigree FY, a US Hispanic family originally from Mexico, demonstrates incomplete penetrance of the DS phenotype while JH, a US Caucasian pedigree, appears to have full penetrance. Similar to that reported by Appukuttan et al, both pedigrees demonstrate variability in the phenotype; affected individuals have either unilateral or bilateral Duane syndrome type I or III and none have type II. In addition, movement abnormalities in some affected individuals suggest dysfunction of muscles innervated by the oculomotor and trochlear nerves as well as the abducens nerve. Linkage analysis reveals that the DS phenotype in both pedigrees maps to the DURS2 locus. The maximum lod score in JH is 2.32 at D2S335 and in FY is 2.10 at D2S2314. Conclusions: The variable phenotype of the affected individuals in these two unpublished DS pedigrees is consistent with the two previous reports and suggests that the DURS2 gene may control cranial nerve development beyond the abducens nerve. These two pedigrees double the number of known DS pedigrees that map to the DURS2 locus and should assist us in the identification of the DURS2 disease gene. Once identified, studies of the function of the DURS2 gene should teach us about abducens development and help us to determine if the clinical findings within the distribution of the oculomotor and trochlear nerves are a primary or secondary phenomenon.
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