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The gene for triphalangeal thumb maps to the subtelomeric region of chromosome 7q

Abstract

Triphalangeal thumb is a developmental anomaly, sometimes dominantly transmitted, characterized by a long, finger–like thumb with three phalanges instead of two. The underlying genetic defect is unknown, but presumably involves genes that regulate the differentiation of the developing forelimb. In two large kindreds with triphalangeal thumb, evidence for linkage to the long arm of chromosome 7 was obtained with a maximum lod score of 12.61. Multipoint linkage and haplotype analysis placed the gene close to the telomere of the long arm. To our knowledge this is the first time that a human gene involved solely in the pathologic morphogenesis of the hand and feet has been localized.

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References

  1. 1

    Qazi, Q. & Kassner, E.G. Triphalangeal thumb. J. med. Genet. 25, 505–520 (1988).

  2. 2

    Tentamy, S. & McKusick, V. The genetics of hand malformations. Birth Defects 14, 3–128 (1978).

  3. 3

    Winter, R.M. & Tickle, C. Syndactylies and Polydactylies: Embryological Overview and Suggested Classification. Eur. J. hum. Genet. 1, 96–104 (1993).

  4. 4

    Lapidus, P.W., Guidotti, F.P. & Coletti, C.J., Report of six cases. Surg. Gynecol. Obste. 77, 178–186 (1943).

  5. 5

    Dolle, P., Izpisua-Belmonte, J.C., Falkenstein, H., Renucci, A. & Duboule, D. Coordinate expression of the murine Hox-5 complex genes during limb pattern formation. Nature 342, 767–772 (1989).

  6. 6

    Dolle, P., Izpisua-Belmonte, J.C., Boncinelli, E. & Duboule, D. The Hox-4.8 gene is localized at the 5' extremity of the Hox-4 complex and is expressed in the most posterior parts of the body during development. Mech. Dev. 36, 3–13 (1991).

  7. 7

    Yokouchi, Y., Sasaki, H. & Kuroiwa, A. Homeobox gene expression correlated with the buriflcation process of limb cartilage development. Nature 353, 443–445 (1991).

  8. 8

    Morgan, B.A., Izpisua-Belmonte, J.C., Duboule, D. & Tabin, C.J. Targeted mlsexpression of Hox-4.6 in the avian limb bud causes apparent homeotic transformation. Nature 358, 236–239 (1992).

  9. 9

    Tabin, C.J. Why we have (only) five fingers per hand: Hox genes and the evolution of paired limbs. Development 116, 289–296 (1992).

  10. 10

    Tabin, C.J., Retinoids, homeoboxes, and growth factors: Toward molecular models for limb development. Cell 66, 199–217 (1991).

  11. 11

    Rosen, D.R. & Brown, R.H., Jr.Dinucleotide repeat polymorphism in the HOX4E locus. Hum. molec. Genet. 2, 617 (1993).

  12. 12

    Weissenbach, J. et al. A second generation linkage map of the human genome. Nature 359, 794–801 (1992).

  13. 13

    Hing, A.V., Helms, C. & Donis-Keller, H. VNTR and microsatellite polymorphisms within the subtelomeric region of 7q. Am. J. hum. Genet. 53, 509–517 (1993).

  14. 14

    Nicolai, J-P.A. & Hamel, B.J.C. A family with complex bilateral polydactyly. J. hand Surg. 13A, 417–419 (1988).

  15. 15

    Radnakrisnna, U., Multani, A.S., Solanki, J.V., Shah, V.C. & Niloufer, J.C. Polydactyly: a study of five generation Indian family. J. med. Genet. 30, 296–299 (1993).

  16. 16

    Warm, A., Di Pietro, C., D'Agrosa, F., Gamblé, M. & Gaboardi, F. Non-opposable triphalangeal thumb in an Italian family. J. med. Genet. 25, 337–339 (1988).

  17. 17

    Vortkamp, A., Gessler, M. & Grzeschik, K-H. GLI3 zinc-finger gene interrupted by translocations in Greig syndrome families. Nature 352, 539–540 (1991).

  18. 18

    Mann, W.R. et al. Fanconi anemia: evidence for linkage heterogeneity on chromosome 20q. Genomics 9, 329–337 (1991).

  19. 19

    Turleau, C. et al. Two patients with interstitial del (14q), one with features of Holt-Oram syndrome: exclusion mapping of Pl (alpha-1-antitrypsin). Ann. Genet. 27, 237–240 (1984).

  20. 20

    Brook, J.D. et al. Holt-Oram syndrome gene is a genetically heterogenerous disease with one locus mapping to human chromosome 12q. Nature Genet. (in the press).

  21. 21

    Logan, C., Willard, H.F., Rommens, J.M. & Joyner, A.L. Localization of the Human Homeobox-Containing Genes, En-1 and En-2. Genomics 4, 206–209 (1989).

  22. 22

    Poole, S.J., Law, M.L., Kao, F-T. & Lau, Y-F. Isolation and Chromosomal Localization of the Human En-2 Gene. Genomics 4, 225–231 (1989).

  23. 23

    Davis, C.A., Holmyard, D.P., Millen, K.J. & Joyner, A.L. Examining pattern formation in mouse, chicken and frog embryos with an En-specific antiserum. Development 111, 287–298 (1991).

  24. 24

    Han, K. & Manley, J.L. Functional domains of the Drosophila Engrailed protein. EMBO J. 12, 2723–2733 (1993).

  25. 25

    Joyner, A.L. & Martin, G.R. En-1 and En-2, two mouse genes with sequence homology to the Drosophila engrailed gene: Expression during development. Genes Dev. 1, 29–38 (1987).

  26. 26

    Martin, G.R., Richman, M., Reinsch, S., Nadeau, J.H. & Joyner, A. Mapping of the two mouse engrailed-like genes: close linkage of En-1 to dominant hemimelia (Dh) on chromosome 1 and of En-2 to hemimelic extra-toes (Hx) on chromosome 5. Genomics 6, 302–308 (1990).

  27. 27

    Knudsen, T.B. & Kochhar, D.M. The role of morphogenetic cell death during abnormal limb-bud outgrowth in mice heterozygous for the dominant mutation hemimelia-extra toe (Hmx). J. Embryol. exp. Morphol. 65, 289–307 (1981).

  28. 28

    Green, M.C. Mouse News Lett. 31, 27 (1964).

  29. 29

    Sweet, H.O. Mouse News Lett. 66, 66 (1982).

  30. 30

    Miller, S.A., Dykes, D.D. & Polesky, H.F. A simple salting out procedure for for extracting DNA from human nucleated cells. Nucl. Acids Res. 16, 1215 (1988).

  31. 31

    Weeks, D.E. & Ott, J. SLINK: a general simulation program for linkage analysis. Am. J. hum. Genet. 47, A204 (1990).

  32. 32

    Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).

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