Abstract
We used probes from the juxtacentromeric region of the chromosome 17 short arm to map three microdeletions in patients with Smith-Magenis syndrome. The commonclinical findings were: speech delay with behavioural problems associated with broad flat midface, brachycephaly, broad nasal bridge and brachydactyly. We demonstrated, using Southern blot analysis (loss of heterozygosity and gene dosage), that all patients were deleted for two p11.2 markers: pYNM 67-R5 (D17S29) and pA10-41 (D17S71). We determined that one breakpoint was located between D17S58 and D17S29 and the other breakpoint distal to D17S71. The possibility that an unstable region, located between the Smith-Magenis syndrome locus and CMT1A a closely located locus, could be involved in the rearrangements associated with these two inherited diseases is discussed.
References
Aldridge J, Kunkel L, Bruns G, Tranthavi U, Lalande R, Brewster T, Moreau E, Wilson M, Bromley W, Roderick T, Latt SA (1984) A strategy to reveal high frequency RFLPs along the human X chromosome. Am J Hum Genet 36:546–564
Barker D, Wright E, Nguyen K, Cannon L, Fain P, Goldgar D, Bishop DT et al. (1987) Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of the chromosome 17. Science 236:1100–1102
Colley AF, Leversha MA, Voullaire LE, Rogers JG (1990) Five cases demonstrating the distinctive behavioural features of chromosome deletion 17(p11.2–p11.2) J Paediatr Child Health 26:17–21
Dobyns WB, Stratton RF, Parke JT, Greenberg F, Nussbaum RF, Ledbetter DH (1983) Miller-Dieker syndrome and monosomy 17p. J Pediatr 102:552–558
Dobyns WB, Curry CJR, Hoyme HE, Turlington L, Ledbetter DH (1991) Clinical and molecular diagnosis of Miller-Dieker syndrome. Am J Hum Genet 48:584–594
Fain PR, Solomon E, Ledbetter DH (1991) Second International Workshop on Human Chromosome 17. Cytogenet Cell Genet 57:65–77
Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 137:266–267
Johnson TL, O'Connel P, Reus BE, Nelson L, Ballard L, White R, Leach RJ (1991) Construction of a physical map of human chromosome 17 using radiation-reduced hybrids. Am J Hum Genet 49:381
Knoll JHM, Nicholls RD, Magenis RE, Graham JM, Lalande M, Latt SA (1989) Angelman and Prader-Willi syndromes share a common deletion but differ in parental origin of the deletion. Am J Hum Genet 32:285–290
Kuwano A, Ledbetter SA, Dobyns WB, Emmanuel SB, Ledbetter DH (1991) Detections of deletions and cryptic translocations in MillerDieker syndrome by in situ hybridization. Am J Hum Genet 49:707–714
Lupski JR, Montes de Oca Luna R, Slaugenhaupt S, Pentao L, Guzzeta V, Trask BJ, Saucedo-Cardenas O, Barker DF, Killian JM, Garcia CA, Chakravarti A, Patel PI (1991) DNA duplication associated with Charcot-Marie-Tooth type 1A. Cell 66:219–232
McAlpine PJ, Feasby TE, Hahn AF, Komarnicki L, James S, Guy C, Dixon M, Qayyum S, Wright J, Coopland G, Lewis M, Kaita H, Phillips S, Wong P, Koopman W, Cox DW, Yee WC (1990) Localization of a locus for Charcot-Marie-Tooth neuropathy type Ia to chromosome 17. Genomics 7:408–415
Middleton-Price HR, Harding AE, Monteiro C, Berciano J, Malcom S (1990) Linkage of hereditary motor and sensory neuropathy type I to the pericentromeric region of chromosome 17. Am J Hum Genet 46:92–94
Moncla A, Livet MO, Auger M, Mattei JF, Mattei MG, Giraud F (1991) A new contiguous gene syndrome. Report of three new cases. J Med Genet 28:627–632
Nakamura Y, Lathrop M, O'Connel P, Leppert M, Barker D, Wright E, Skolnick M, Kondoleon S, Litt M, Lalouel JM, White R (1988) A mapped set of DNA markers for human chromosome 17. Genomics 2:302–309
Raeymaekers P, Timmerman V, Dejonghe P, Swerts L, Gheuens J, Martin JJ, Muylle L, De Winter J, Vandenberghe A, Van Broeckhoven C (1989) Localization of the mutation in an extended family with Charcot-Marie-Tooth neuropathy (HMSN 1). Am J Hum Genet 45:953–958
Schmickel RD (1986) Contiguous gene syndromes: a component of recognizable syndromes. J Pediatr 109:231–241
Smith ACM, McGavran J, Robinson J, Waldstein G, McFarcane L, Zonana R, Reiss J, Lahr M, Allen L, Magenis E (1986) interstitial deletion of (17)(p11.2) in nine patients. Am J Med Genet 24:393–414
Stratton RF, Dobyns WB, Airhart SC, Ledbetter DH (1984) New chromosomal syndrome: Miller-Dieker syndrome and monosomy 17p13. Hum Genet 67:193–200
Stratton RF, Dobyns WB, Greenberg F, De Sana JB, Moore C, Fidone G, Runge GHM, Feldman P, Sekhon G, Pauli RM, Ledbetter DH (1986) Interstitial deletions of (17)(p11.2) report of six additional patients with a new chromosome deletion syndrome. Am J Med Genet 24:421–432
Vance JM, Nicholson GA, Yamahoka LH, Stajich J, Stewart CS, Speer MC, Hung WH, et al (1989) Linkage of Charcot-Marie-Tooth neuropathy type Ia to chromosome 17. Exp Neurol 104:186–189
Van Tuinen P, Rich DC, Summers KM, Ledbetter DH (1987) Regional mapping pannel for human chromosome 17: application to neurofibromatosis type I. Genomics 1:374–381
Weber JL, Kwitek AE, May PE, Wallace MR, Collins FS, Ledbetter DH (1990) Dinucleotide repeat polymorphisms at the D17S250 and D17S261 loci. Nucleic Acids Res 18:4640
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Moncla, A., Piras, L., Arbex, O.F. et al. Physical mapping of microdeletions of the chromosome 17 short arm associated with Smith-Magenis syndrome. Hum Genet 90, 657–660 (1993). https://doi.org/10.1007/BF00202487
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DOI: https://doi.org/10.1007/BF00202487