Abstract
Subtelomeric chromosomal abnormalities are emerging as an important cause of human genetic disorders. The scope of this investigation was to screen a selected group of children with idiopathic mental retardation for subtelomeric anomalies using the multiprobe telomeric FISH method and also to develop and test a new assay, the MAPH telomeric assay, in the same group of patients. The new MAPH telomeric assay uses the recently published MAPH methodology that permits the measurement of locus copy number by hybridisation with a specifically designed set of probes located at the end of human chromosomes. Seventy patients with idiopathic mental retardation have been screened using the established multiprobe telomeric FISH assay and the new MAPH telomeric assay, for all telomeres. One patient with de novo 8p subtelomeric deletion was identified. The new MAPH telomeric assay confirmed the same results in both normal and abnormal samples. This is the first description of the use of MAPH methodology to detect chromosomal imbalances near the telomeres in idiopathic mentally retarded patients. The new MAPH telomeric assay offers a new, fast, accurate and cost effective diagnostic tool to detect chromosomal imbalances near telomeres in mentally retarded patients, as well as the characterisation of known chromosomal abnormalities, spontaneous recurrent miscarriages, infertility, hematological malignancies, preimplantation genetic diagnosis, and other fields of clinical and research interests.
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Birch HG, Richardson SA, Baird D, Horobin G, Ilsley R . Mental subnormality in the community: a clinical and epidemiological study Baltimore: Williams and Wilkins 1970
Gustavson KH, Hagberg B, Hagberg G, Sars K . Severe mental retardation in a Swedish country: II, etiologic and pathogenetic aspects of children born 1959–1970 Neuropadiatrie 1977 8: 293–304
Laxova R, Ridler MAC, Bowen-Bravery M . An etiological survey of the severely retarded Hertfordshire children who were born between January 1, 1965 and December 31, 1967 Am J Med Genet 1977 1: 75–86
Lamont MA, Dennis NR . Aetiology of mild mental retardation Arch Dis Child 1988 63: 1032–1038
Einfeld SL . Clinical assessment of 4500 developmentally delayed individuals J Med Defic Res 1984 28: 129–142
Wilkie AOM . Detection of cryptic chromosomal abnormalities in unexplained mental retardation: a general strategy using hypervariable subtelomeric DNA polymorphisms Am J Hum Genet 1993 53: 688–701
Lamb J, Wilkie AOM, Harris PC et al. Detection of breakpoints in submicroscopic chromosomal translocation, illustrating an important mechanism for genetic disease Lancet 1989 ii: 819–824
Flint J, Wilkie AO, Buckle VJ, Winter RM, Holland AJ, McDermid HE . The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation Nat Genet 1995 9: 132–140
Slavotinek A, Rosenberg M, Knight S et al. Screening for submicroscopic chromosome rearrangements in children with idiopathic mental retardation using microsatellite markers for the chromosome telomeres J Med Genet 1999 36: 405–411
Knight SJL, Horsley SW, Regan R et al. Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres Eur J Hum Genet 1997 5: 1–8
National Institute of Health, Institute of Molecular Medicine . Collaboration. A complete set of telomeric probes and their clinical application Nat Genet 1996 14: 86–89
Knight SJL, Regan R, Nicod A et al. Subtle chromosomal rearrangements in children with unexplained mental retardation The Lancet 1999 354: 1676–1681
Knight SJL, Flint J . Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis J Med Genet 2000 37: 401–409
Armour JAL, Sismani C, Patsalis PC, Cross G . Measurement of locus copy number by hybridization with amplifiable probes Nucleic Acids Res 2000 28: 2 605–609
Patsalis PC, Sismani C, Hettinger J et al. Molecular screening of fragile X (FRAXA) and FRAXE mental retardation syndromes in the Hellenic population of Greece and Cyprus: Incidence, genetic variation and stability Am J Med Genet 1999 84: 184–190
Baird DM, Royle NJ . Sequences from higher primates orthologous to the human Xp/Yp telomere junction region reveal gross rearrangements and high levels of divergence Hum Mol Genet 1997 13: 2291–2299
Maniatis T, Sambrook J, Fritsch EF . Molecular Cloning Cold Spring Harbor Laboratory Press 1989
Borgione E, Giudice ML, Gelesi O et al. How microsatellite analysis can be exploited for subtelomeric chromosomal rearrangements analysis in mental retardation J Med Genet 2001 38: E1
Youngman S, Bates GP, Williams S et al. The telomeric regions on 13p, 15p, 21p, and 22p Genomics 1992 14: 350–356
Wright TJ, Wijmenga C, Clark LN, Frants RR, Williamson R, Hewitt JE . Fine Mapping of the FSHD gene region orientates the rearranged fragment detected by the probe p13E-11 Hum Mol Genet 1993 2: 1673–1678
Knight SJL, Lese CM, Precht KS et al. An optimized set of human telomere clones for studing telomere integrity and architecture Am J Hum Genet 2000 67: 320–332
Nesslinger NJ, Gorski JL, Kurczynski TW et al. Clinical characterization of seven patients with deletions of chromosome 22q13.3 Am J Hum Genet 1994 54: 464–472
Kvaloy K, Galvagni F, Brown WR . The sequence organization of the long arm pseudoautosomal region of the human sex chromosomes Hum Mol Genet 1994 3: 771–778
Giraudeau F, Aubert D, Young I et al. Molecular cytogenetic detection of 1p36.3 J Med Genet 1997 34: 314–317
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We would like to acknowledge The Wellcome Trust and the Cyprus Institute of Neurology and Genetics for financial support, Dr V Anastasiadou and Dr G Stylianidou for their assistance.
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Sismani, C., Armour, J., Flint, J. et al. Screening for subtelomeric chromosome abnormalities in children with idiopathic mental retardation using multiprobe telomeric FISH and the new MAPH telomeric assay. Eur J Hum Genet 9, 527–532 (2001). https://doi.org/10.1038/sj.ejhg.5200670
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DOI: https://doi.org/10.1038/sj.ejhg.5200670
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