Summary
The results of an epidemiological survey on Huntington's disease in the Lazio Region, Central Italy, and of linkage studies in a subset of families are reported. From a total of 99 ascertained families and 491 patients, a prevalence of 25.6 × 10−6 was obtained, with distributions of age at onset and age at death similar to those described in the literature. No relationship with the sex of the transmitting parent was observed. Analysis of 10 chromosome 4 restriction fragment length polymorphisms in 11 families showed consistent linkage between the genetic loci D4S10, D4S43 and D4S95, and the disease. A recombination rate of 0.08 for D4S10 markers was obtained in this sample. Allelic frequencies of DNA markers in the general population are also reported.
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Bakker E, Skraastad KI, Fisser-Groen YM, Ommen GJB van, Pearson PL (1987) Two additional RFLPs at the D4S10 locus, useful for Huntington's disease (HD)-family studies. Nucleic Acids Res 15:9100
Brambilla C, Frontali M, Malaspina P, Rossi C (1990) On the estimation of the age at onset distribution in Huntington's chorea using the EM algorithm. Ann Hum Genet (in press)
Dempster AP, Laird NM, Rubin DB (1977) Maximum likelihood estimation from incomplete data via EM algorithm (with discussion). J R Statist Soc Biol 39:1–38
Di Maio L, Mengano A, Maggio MA, De Michele G, Campanella G (1984) Paternal and maternal transmission in Huntington's disease. Acta Neurol 39:447–450
Farrer LA, Myers RH, Cupples LA, Conneally PM (1988) Considerations in using linkage analysis as a presymptomatic test for Huntington's disease. J Med Genet 25:577–588
Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13
Folstein SE, Chase GA, Wahl WE, McDonnell AM, Folstein MF (1987) Huntington disease in Maryland: clinical aspects and racial variation. Am J Hum Genet 41:168–179
Gilliam TC, Bucan M, MacDonald ME, Zimmer M, Haines J, Cheng SV, Pohl TM, Myers RH, Whaley WL, Allitto B, Faryniarz A, Wasmuth JJ, Frischauf AM, Conneally PM, Gusella JF (1987a) A DNA segment encoding two genes very tightly linked to Huntington disease gene. Science 238:950–952
Gilliam TC, Tanzi RE, Haines JL, Bonner TI, Faryniarz AG, Hobbs WJ, MacDonald ME, Cheng SV, Folstein SE, Conneally PM, Wexler NS, Gusella JF (1987b) Localization of the Huntington's disease gene to a small segment of chromosome 4 flanked by D4S10 and the telomere. Cell 50:565–571
Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi R, Watkins PC, Ottina K, Wallace MR, Sakaguchi AY, Young AB, Shoulson I, Bonilla E, Martin JB (1983) A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306:234–238
Gusella JF, Gilliam TC, Tanzi RE, MacDonald ME, Cheng SV, Wallace M, Haines J, Conneally PM, Wexler NS (1986) Molecular genetics of Huntington's disease. Cold Spring Harb Symp Quant Biol 51:359–364
Hayden MR (1981) Huntington's chorea. Springer, Berlin Heidelberg New York
Hayden MR, Hewitt J, Maresca A, Langlois S (1987) A polymorphic DNA probe located to human chromosome 4p16 (D4S62). Nucleic Acids Res 15:3938
Jarman AP, Nicholls RD, Weatherall DJ, Clegg JB, Higgs DR (1986) Molecular characterization of a hypervariable region downstream of the human alpha-globin gene cluster. EMBO J 5:1857–1863
Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observation. J Am Statist Assoc 53:457–481
MacDonald ME, Cheng SV, Zimmer M, Haines JL, Poutska A, Allitto B, Smith B, Whaley WL, Romano DM, Jagadeesh J, Myers RH, Lehrach H, Wasmuth JJ, Frischauf A, Gusella JF (1989) Clustering of multiallele DNA markers near the Huntington's disease gene. J Clin Invest 84:1013–1016
Myers RH, Goldman D, Bird ED, Sax DS, Merril CR, Schoenfeld M, Wolf PA (1983) Maternal transmission in Huntington disease. Lancet I:208–210
Newcombe RG, Walker DA, Harper PS (1981) Factors influencing age at onset and duration of survival in Huntington's chorea. Ann Hum Genet 45:387–396
Ott J (1974) Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet 26:588–597
Quarrell OWJ, Tyler A, Upadhyaya M, Meredith AL, Youngman AL, Harper PS (1987) Exclusion testing for Huntington's disease in pregnancy with a closely linked DNA marker. Lancet I:1281–1283
Reed TE, Chandler JH (1958) Huntington's chorea in Michigan. I. Demography and genetics. Am J Hum Genet 10:201–225
Smith B, Skarecky D, Bengtsson U, Magenis RE, Carpenter N, Wasmuth JJ (1988) Isolation of DNA markers in the direction of the Huntington disease gene from the G8 locus. Am J Hum Genet 42:335–344
Walker DA, Harper PS, Wells CEC, Tyler A, Davies K, Newcombe RG (1981) Huntington's chorea in South Wales. A genetic and epidemiologic study. Clin Genet 19:213–221
Wasmuth JJ, Hewitt J, Smith B, Allard D, Haines JL, Skarecky D, Partlow E, Hayden MR (1988) A highly polymorphic locus very tightly linked to the Huntington's disease gene. Nature 332:734–736
Went LN, Vegter-Van Der Vlies M, Bruyn GW, Volkers WS (1983) Huntington's chorea in Netherlands. The problem of enetic heterogeneity. Ann Hum Genet 47:205–214
Youngman S, Sarfarazi M, Quarrell OW, Conneally PM, Gibbons K, Harper PS, Shaw DJ, Tanzi RE, Wallace MR, Gusella JF (1986) Studies of a DNA marker (G8) genetically linked to Huntington disease in British families. Hum Genet 73:333–339
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Frontali, M., Malaspina, P., Rossi, C. et al. Epidemiological and linkage studies on Huntington's disease in Italy. Hum Genet 85, 165–170 (1990). https://doi.org/10.1007/BF00193190
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DOI: https://doi.org/10.1007/BF00193190