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The DURS1 locus was defined by the presence of cytogenetic abnormalities (abnormal chromosome number and/or structure) on the q arm of Chromosome 8 in individuals manifesting Duane syndrome. No Duane Syndrome family to date has been reported to map to this locus by linkage analysis.
The first reported individual1 had Duane Syndrome, branchio-oto-renal (BOR) syndrome, hydrocephalus, and trapezius muscle aplasia associated with a de novo 8q12.2-q21.2 deletion. The second individual2 had Duane Syndrome Type 1, microcephaly, mental retardation, and dysmorphic features and an insertion of 8q13-q21.2 onto 6q25 with an associated deletion of 8q13. The third patient had DS and hypoplastic external genitalia and a reciprocal translocation of t(6;8)(q26;q13)3 and Pizzuti et al in 20024 determined that the chr 8 breakpoint in this individual was between exons 1 and 2 of a carboxypeptidase gene, CPAH. Although they did not identify any mutations in this gene in 18 sporadic (isolated) Duane syndrome participants, CPAH, a gene involved in peptide processing of the brain, still remains a good candidate gene for this disorder.
More recently, Anwar et al5 described patients with trisomy 8 and Duane syndrome.
Please contact Caroline Andrews to obtain further information on the genetic studies that we are undertaking and if you are interested in enrolling a patient or participating yourself.
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References
Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor, Johns Hopkins University, last edit date 3/3/2005 (entry number 126800). Home page: http://www3.ncbi.nlm.nih.gov/Omim/.
1. Vincent C, Kalatzis V, Compain S, Levilliers J, Slim R, Graia F, Pereira ML, Nivelon A, Croquette MF, Lacombe D, et al.. A proposed new contiguous gene syndrome on 8q consists of branchio-oto-renal (BOR) syndrome, Duane syndrome, a dominant form of hydrocephalus and trapeze aplasia; implications for the mapping of the BOR gene. Human Molecular Genetics 3, 1859-1866 (1994).
2. Calabrese G, Stuppia L, Morizio E, Guanciali Franchi P, Pompetti F, Mingarelli R, Marsilio T, Rocchi M, Gallenga PE, Palka G, Dallapiccola B.. Detection of an insertion deletion of region 8q13-q21.2 in a patient with Duane syndrome: implications for mapping and cloning a Duane gene. European Journal of Human Genetics 6, 187-193 (1998).
3. Calabrese G, Telvi L, Capodiferro F, Morizio E, Pizzuti A, Stuppia L, Bordoni R, Ion A, Fantasia D, Mingarelli R, Palka G.. Narrowing the Duane syndrome critical region at chromosome 8q13 down to 40 kb. Eur J Hum Genet 8, 319-24 (2000).
4. Pizzuti A, Calabrese G, Bozzali M, Telvi L, Morizio E, Guida V, Gatta V, Stuppia L, Ion A, Palka G, Dallapiccola B.. A peptidase gene in chromosome 8q is disrupted by a balanced translocation in a duane syndrome patient. Invest Ophthalmol Vis Sci 43, 3609-12 (2002).
5. Anwar, S., Bradshaw, K. & Vivian, A.J. Ophthalmic manifestations of trisomy 8 mosaic syndrome. Ophthalmic Genet 19, 81-6 (1998).
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