Abstract
Four DNA markers on the distal long arm of chromosome 4 have been analyzed for their linkage to facioscapulohumeral muscular dystrophy locus (FSHD) in a series of 16 Italian families. We found that, in two families, the disease is not linked to the 4q35 markers, indicating the presence of genetic heterogeneity among Italian FSHD families. Linkage analysis in the remaining families supports the order cen-D4S171-D4S163-D4S139-D4S810-FSHD-qter, in agreement with the physical map from the literature. EcoRI digestion and hybridization with the distal marker p13E-11 (D4S810)Footnote 1 detected DNA rearrangements in the affected members of both sporadic and familial cases of FSHD, with family-specific fragments ranging in size between 15 kb and 28 kb. In three sporadic FSHD cases, the appearance of a new “small” fragment not present in either parent was clearly associated with the development of FSHD disease. However, in the familial cases analyzed, we observed two recombinations between all four 4q35 markers and the disease locus in apparently normal subjects, leaving open the possibility of nonpenetrance of the FSHD mutation.
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Notes
The locus D4S810 corresponding to probe p13E-11 has been recently renamed D4F104S1.
References
DiRienzo A, Felicetti L, Novelletto A, Forteleoni G, Colombo B (1985) Frequency and types of deletional alpha+-thalassemia in Northern Sardinia. Hum Genet 71:147–149
Gilbert JR, Stajich JM, Speer MC, Vance JM, Stewart CS, Yamaoka LH, Samson F, et al (1992) Linkage studies in facioscapulohumeral muscular dystrophy (FSHD). Am J Hum Genet 51:424–427
Gilbert JR, Stajich JM, Wall S, Carter SC, Qiu H, Vance JM, Stewart CS, et al (1993) Evidence for heterogeneity in facioscapulohumeral muscular dystrophy (FSHD). Am J Hum Genet 53:401–408
Lathrop GM, Lalouel JM, Julier C, Ott J (1984) Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci USA 81:3443–3446
Lunt PW, Harper PS (1991) Genetic counselling in facioscapulohumeral muscular dystrophy. J Med Genet 28:655–664
Lunt PW, Noades JG, Upadhyaya M, Sarfarazi M, Harper PS (1988) Evidence against location of the gene for facioscapulohumeral muscular dystropy on the distal long arm of chromosome 14. J Neurol Sci 88:287–292
Mathews KD, Mills KA, Bosch EP, Jonasescu VV, Wiles KR, Buetow KH, Murray JC (1992) Linkage localization of facioscapulohumeral muscular dystrophy (FSHD) in 4q35. Am J Hum Genet 51:428–431
Mills KA, Buetow KH, Xu Y, Ritty TM, Mathews KD, Bodrug SE, Wijmenga C, et al (1992) Genetic and physical mapping on chromosome 4 narrows the localization of the gene for facioscapulohumeral muscular dystrophy (FSHD). Am J Hum Genet 51:423–439
Milner EC, Lotshaw CL, Willems van Dijk K, Charmley P, Concannon P, Shroeder HW Jr (1989) Isolation and mapping of a polymorphic DNA sequence pH30 on chromosome 4 (HGM provisional no. D4S139). Nucleic Acids Res 17:4002
Neuweiler J, Ruvolo V, Baum H, Grzeschik KH, Balasz I (1990) Isolation and characterization of a hypervariable region (D4S163) on chromosome 4. Nucleic Acids Res 18:691
Ott J (1978) A simple scheme for the analysis of HLA linkages in pedigrees. Ann Hum Genet 42:255–257
Ott J (1983) Linkage analysis and family classification under heterogeneity. Ann Hum Genet 47:311–320
Padberg G (1982) Facioscapulohumeral disease. MD thesis, University of Leiden, Leiden
Padberg GW, Lunt PW, Koch M, Fardeau M (1991) Diagnostic criteria for facioscapulohumeral muscular dystrophy. Neuromuscul Disord 1:231–234
Sarfarazi M, Wijmenga C, Upadhyaya M, Weiffenbach B, Hyser C, Mathews K, Murray J, et al (1992) Regional mapping of facioscapulohumeral muscular dystrophy gene on 4q35: combined analysis of an international consortium. Am J Hum Genet 51:396–403
Upadhyaya M, Lunt P, Sarfarazi M, Broadhead W, Farnham J, Harper PS (1992) The mapping of chromosome 4q markers in relation to facioscapulohumeral muscular dystrophy (FSHD). Am J Hum Genet 51:404–410
Weber JL, May PE (1990) Dinucleotide repeat polymorphism at the D4S171 locus. Nucleic Acids Res 18:2202
Weiffenbach B, Bagley R, Falls K, Hyser C, Storvick D, Jacobsen SJ, Schultz P, et al (1992) Linkage analyses of five chromosome 4 markers localizes the facioscapulohumeral muscular dystrophy (FSHD) gene to distal 4q35. Am J Hum Genet 51:416–423
Weiffenbach B, Dubois J, Storvick D, Tawil R, Jacobsen SJ, Gilbert J, Wijmenga C, et al (1993) Mapping the facioscapulohumeral muscular dystrophy gene is complicated by chromosome 4q35 recombination events. Nature Genet 4:165–169
Wijmenga C, Sandkuijl LA, Moerer P, Boorn N van der, Bodrug SE, Ray PN, Brouwer OF, et al (1992a) Genetic linkage map of facioscapulohumeral muscular dystrophy and five polymorphic loci on chromosome 4q35-qter. Am J Hum Genet 51:411–415
Wijmenga C, Hewitt JE, Sandkuijl LA, Clark LN, Wright TJ, Dauwerse HG, Gruter AM, et al (1992b) Chromosome 4q DNA rearrangements associated with facioscapulohumeral muscular dystrophy. Nature Genet 3:26–30
Winokur ST, Schutte B, Weiffenbach B, Washington SS, McElligott D, Chakravarti A, Wasmuth JH, Altherr MR (1993) A radiation hybrid map of 15 loci on the distal long arm of chromosome 4, the region containing the gene responsible for facioscapulohumeral muscular dystrophy (FSHD). Am J Hum Genet 53:874–880
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Cacurri, S., Deidda, G., Piazzo, N. et al. Chromosome 4q35 haplotypes and DNA rearrangements segregating in affected subjects of 19 Italian families with facioscapulohumeral musculatur dystrophy (FSHD). Hum Genet 94, 367–374 (1994). https://doi.org/10.1007/BF00201595
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DOI: https://doi.org/10.1007/BF00201595