Abstract
Patients with interstitial deletions of the long arm of chromosome 13 may have widely varying phenotypes. From cytogenetic analysis, we have postulated that there is a discrete region in 13q32 where deletion leads to a syndrome of severe malformations, including digital and brain anomalies. To test this hypothesis at the molecular level, we have studied the deletions in 17 patients; 5 had severe malformations, while the remaining 12 had only minor malformations. Our results indicate that the deletions in the severely affected patients all involve an overlapping region in q32, while the deletions in the mildly affected patients include some, but not all, of this overlapping region. Our findings are consistent with the hypothesis that the severely malformed 13q- phenotype results from the deletion of a critical region in 13q32. This region is presently defined as lying between D13S136 and D13S147 and is on the order of 1 Mb in size.
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- Bottani A., Xie Y. G., Binkert F., Schinzel A. A case of Hirschsprung disease with a chromosome 13 microdeletion, del(13)(q32.3q33.2): potential mapping of one disease locus. Hum Genet. 1991 Oct;87(6):748–750. doi: 10.1007/BF00201741. [DOI] [PubMed] [Google Scholar]
- Brown S., Gersen S., Anyane-Yeboa K., Warburton D. Preliminary definition of a "critical region" of chromosome 13 in q32: report of 14 cases with 13q deletions and review of the literature. Am J Med Genet. 1993 Jan 1;45(1):52–59. doi: 10.1002/ajmg.1320450115. [DOI] [PubMed] [Google Scholar]
- Carmichael A., Addy D. P., Shortland-Webb W. R., Cameron A. H., Davies I. C. 13q- syndrome. Family study. Arch Dis Child. 1977 Dec;52(12):972–974. doi: 10.1136/adc.52.12.972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cowell J. K., Mitchell C. D. A somatic cell hybrid mapping panel for regional assignment of human chromosome 13 DNA sequences. Cytogenet Cell Genet. 1989;52(1-2):1–6. doi: 10.1159/000132827. [DOI] [PubMed] [Google Scholar]
- Fischer S. G., Cayanis E., Russo J. J., Sunjevaric I., Boukhgalter B., Zhang P., Yu M. T., Rothstein R., Warburton D., Edelman I. S. Assembly of ordered contigs of cosmids selected with YACs of human chromosome 13. Genomics. 1994 Jun;21(3):525–537. doi: 10.1006/geno.1994.1311. [DOI] [PubMed] [Google Scholar]
- Hennies H. C., Reis A. Three dinucleotide microsatellite polymorphisms on human chromosome 13. Hum Mol Genet. 1993 Jan;2(1):87–87. doi: 10.1093/hmg/2.1.87. [DOI] [PubMed] [Google Scholar]
- Kennerknecht I., Klett C., Hameister H. Assignment of the human gene propionyl coenzyme A carboxylase, alpha-chain, (PCCA) to chromosome 13q32 by in situ hybridization. Genomics. 1992 Oct;14(2):550–551. doi: 10.1016/s0888-7543(05)80269-1. [DOI] [PubMed] [Google Scholar]
- Nichols W. W., Miller R. C., Hoffman E., Albert D., Weichselbaum R. R., Nove J., Little J. B. Interstitial deletion of chromosome 13 and associated congenital anomalies. Hum Genet. 1979 Nov;52(2):169–173. doi: 10.1007/BF00271569. [DOI] [PubMed] [Google Scholar]
- Petrukhin K. E., Speer M. C., Cayanis E., Bonaldo M. F., Tantravahi U., Soares M. B., Fischer S. G., Warburton D., Gilliam T. C., Ott J. A microsatellite genetic linkage map of human chromosome 13. Genomics. 1993 Jan;15(1):76–85. doi: 10.1006/geno.1993.1012. [DOI] [PubMed] [Google Scholar]
- Samec S., Clarkson S. G., Blaschak J., Chakravarti A., Morris M. A., Scherly D., Antonarakis S. E. Dinucleotide repeat polymorphism within ERCC5 gene. Hum Mol Genet. 1994 Jan;3(1):214–214. doi: 10.1093/hmg/3.1.214-a. [DOI] [PubMed] [Google Scholar]
- Slater H., Shaw J. H., Dawson G., Bankier A., Forrest S. M. Maternal uniparental disomy of chromosome 13 in a phenotypically normal child. J Med Genet. 1994 Aug;31(8):644–646. doi: 10.1136/jmg.31.8.644. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takahashi E., Shiomi N., Shiomi T. Precise localization of the excision repair gene, ERCC5, to human chromosome 13q32.3-q33.1 by direct R-banding fluorescence in situ hybridization. Jpn J Cancer Res. 1992 Nov;83(11):1117–1119. doi: 10.1111/j.1349-7006.1992.tb02731.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tranebjaerg L., Nielsen K. B., Tommerup N., Warburg M., Mikkelsen M. Interstitial deletion 13q: further delineation of the syndrome by clinical and high-resolution chromosome analysis of five patients. Am J Med Genet. 1988 Apr;29(4):739–753. doi: 10.1002/ajmg.1320290403. [DOI] [PubMed] [Google Scholar]
- Trask B. J., Massa H., Kenwrick S., Gitschier J. Mapping of human chromosome Xq28 by two-color fluorescence in situ hybridization of DNA sequences to interphase cell nuclei. Am J Hum Genet. 1991 Jan;48(1):1–15. [PMC free article] [PubMed] [Google Scholar]
- Washington S. S., Warburton D., Chakravarti A. Report and abstracts of the Second International Workshop on Human Chromosome 13 Mapping 1994. Cytogenet Cell Genet. 1995;70(1-2):1–22. doi: 10.1159/000133982. [DOI] [PubMed] [Google Scholar]
- Weber J. L., May P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed] [Google Scholar]
- Weissenbach J., Gyapay G., Dib C., Vignal A., Morissette J., Millasseau P., Vaysseix G., Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. doi: 10.1038/359794a0. [DOI] [PubMed] [Google Scholar]
- Wilroy R. S., Jr, Summitt R. L., Martens P., Gooch W. M., 3rd, Hood C., Wiser W. Partial monosomy and partial trisomy for different segments of chromosome 13 in several individuals of the same family. Birth Defects Orig Artic Ser. 1976;12(5):161–167. [PubMed] [Google Scholar]