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From Genetic Research into Clinical Practice

Published online by Cambridge University Press:  01 August 2014

B. Dallapiccola ,
I. Torrente ,
R. Mingarelli  and
G. Novelli
B. Dallapiccola*
Affiliation:
Cattedra di Genetica Medica e Umana, Università Tor Vergata& CSS – Mendel Institute, Rome, Italy
I. Torrente
Affiliation:
Cattedra di Genetica Medica e Umana, Università Tor Vergata& CSS – Mendel Institute, Rome, Italy
R. Mingarelli
Affiliation:
Cattedra di Genetica Medica e Umana, Università Tor Vergata& CSS – Mendel Institute, Rome, Italy
G. Novelli
Affiliation:
Cattedra di Genetica Medica e Umana, Università Tor Vergata& CSS – Mendel Institute, Rome, Italy
*
Chair of Medical Genetics, University of Tor Vergata, Via di Tor Vergata n. 135, 00133 Rome, Italy

Abstract

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The present genome era is characterized by speedy progress and prompt transfer of results into clinical practice. This creates the need for rapid disclosure of results and renewal of laboratory's protocols. Molecular cytogenetics has provided and increased ability to identify chromosomes, correlate chromosome structure with gene location, find out cryptic aberrations, and detect specific DNA sequences. These advances have allowed the confident discovery of a number of contiguous gene syndromes. The positional cloning and positional candidate strategies have greatly expedited the search process of disease genes, and become relevant methods for genes' discovery. Understanding the molecular basis of diseases has shown an unpredicted wide genetic heterogeneity, which has splitted single disorders into many clinically similar conditions, and added complexity to the nosology of human diseases. The opposite process, allelism, where clinical diversity results from allelic mutations, has lumped together many distinct disorders, by showing that different clinical entities are not necessarily due to mutations in different genes. Dynamic mutations have provided the molecular understanding of interindividual and intrafamilial variability including anticipation, in a number of diseases. The discovery of distinct correlations between the molecular pattern and disease severity is providing a unique opportunity for using molecular results to assess the clinical outcome. Diagnostic, presymptomatic and predictive molecular testing are becoming widely used and provide enormous opportunities for improving the lot of our patients.

Keywords

Spinal muscolar atrophyMolecular cytogeneticsContiguous gene syndromesWilliams syndromeDiGeorge/velocardiofacial syndromeGenetic heterogeneityDynamic mutationsGenetic testing
Type
Research Article
Information
Acta geneticae medicae et gemellologiae: twin research , Volume 46 , Issue 3 , July 1997 , pp. 139 - 146
Copyright
Copyright © The International Society for Twin Studies 1999

References

REFERENCES

1.Campbell, L, Potter, A, Ignatius, J, Dubowitz, V, Davies, K (1997): Genomic variation and gene conversion in spinal muscular atrophy: implications for disease process and clinical phenotype. Am J Hum Genet 61: 40–50.Google Scholar
2.Capon, F, Melchionda, S, Gennarelli, M, Lo Cicero, S, Giacanelli, M, Novelli, G, Dallapiccola, B (1993): A tool for the molecular analysis of an early lethal disease: slide-PCR in spinal muscular atrophy patients. Molecular and Cellular Probes 7: 221–226.Google Scholar
3.Capon, F, Levato, C, Busaglia, E, Lo Cicero, S, Tizzano, EF, Baiget, M, Silani, V, Pizzuti, A, Novelli, G, Dallapiccola, B (1996): Deletion analysis of simple tandem repeat loci phisically linked to the spinal muscular atrophy locus. Hum Mutat 7: 198–201.Google Scholar
4.Capon, F, Levato, C, Semprini, S, Pizzuti, A, Merlini, L, Novelli, G, Dallapiccola, B (1996): Deletion analysis of SMN and NAIP genes in spinal muscular atrophy in Italian families. Muscle & Nerve 19: 378–380.Google Scholar
5.Capon, F, Levato, C, Merlini, L, Angelini, C, Mostacciuolo, ML, Politano, L, Novelli, G, Dallapiccola, B (1996): Discordant clinical outcome in type III spinal muscular atrophy sibships showing the same deletion pattern. Neuromusc Dis 6: 261–264.Google Scholar
6.Calabrese, G, Mingarelli, R, Francalanci, P, Boldrini, R, Palka, G, Bosman, C, Novelli, G, Dallapiccola, B (1996): Diagnosis of DiGeorge syndrome in nuclei released from archival autoptic heart specimens using fluorescent in situ hybridisation. Hum Genet 97: 414–417.CrossRefGoogle Scholar
7.Collins, FS (1995): Positional cloning moves from perditional to traditional. Nature Genet 9: 347–370.CrossRefGoogle ScholarPubMed
8.Dallapiccola, B, Mingarelli, R, Novelli, G (1995): The link between cytogenetics and mendelism. Biomed Pharmacother 49: 83–93.CrossRefGoogle ScholarPubMed
9.Dallapiccola, B, Pizzuti, A, Novelli, G (1996): How many breaks do we need to CATCH on 22q11? Am J Hum Genet 59: 7–11.Google ScholarPubMed
10.Delaroche, I, Sabani, M, Calabrese, G, Mingarelli, R, Palka, G, Dallapiccola, B (1995): Fetal translocation between chromosomes 2, 18 and 21 resolved by FISH. Prenat Diagn 15: 278–281.CrossRefGoogle Scholar
11.Ewart, AK, Morris, CA, Atkinson, DL, Jin, W, Sternes, K, Spallone, P, Stock, D, Leppert, M, Keating, MT (1993): Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nature Genet 5: 11–16.Google Scholar
12.Flint, J, Wilkie, AOM, Buckle, VJ, Winter, RM, Holland, AJ, McDermid, HE (1995): The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nature Genet 9: 132–139.CrossRefGoogle ScholarPubMed
13.Frangiskakis, JM, Ewart, AK, Morris, CA, Mervis, CB, Bertrand, J, Robinson, BF, Klein, BP, Ensing, GJ, Everett, LA, Green, ED, Proschel, C, Gutowski, NJ, Noble, M, Atkinson, DL, Odelberg, SJ, Keating, MT (1996): LIM-kinase 1 hemizygosity implicated in impaired visuospatial constructive cognition. Cell 86 (1.: 59–69.Google Scholar
14.Fu, YH, Kuhl, PD, Pizzuti, A, Pieretti, M, Sutcliffe, JS, Richards, S, Verkerk, AJMH, Golden, JJA, Fenwick, RG, Warren, ST, Oostra, BA, Nelson, DL, Caskey, CT (1991): Variation of CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67: 1047–1058.CrossRefGoogle ScholarPubMed
15.Gennarelli, M, Novelli, G, Andreasi Bassi, F, Martorell, L, Cornet, M, Menegazzo, E, Mostacciuolo, ML, Martinez, JM, Angelini, C, Pizzati, A, Baiget, M, Dallapiccola, B (1996): Prediction of myotonic dystrophy clinical severity based on number of intragenic (CTG)n trinucleotide repeats. Am J Med Genet 65: 342–347.Google Scholar
16.Harper, PS (1997): What we do mean by genetic testing. J Med Genet 34: 749–752.CrossRefGoogle ScholarPubMed
17.Hubbard, R, Lewontin, RC (1996): Pitfalls of genetic testing. New Engl J Med 334: 1192–1193.CrossRefGoogle ScholarPubMed
18.Le Beau, M (1996): One FISH, two FISH, red FISH, blue FISH. Nature Genet 12: 341–344.CrossRefGoogle ScholarPubMed
19.Ledbetter, DH (1992): The “colorizing” of cytogenetics: is it ready for prime time? Hum Mol Genet 5: 297–299.Google Scholar
20.Ledbetter, DH, Engel, E (1995): Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis. Hum Mol Genet 4:1757–1764.CrossRefGoogle ScholarPubMed
21.Mari, A, Amati, F, Mingarelli, R, Giannotti, A, Sebastio, G, Colloridi, V, Novelli, G, Dallapiccola, B (1995): Analysis of the elastin gene in 60 patients with clinical diagnosis of Williams syndrome. Human Genet 96: 444–448.Google Scholar
22.Mehes, K (1996): Classical clinical genetics in the era ot molecular genetics. Am J Med Genet 61: 394–395.Google Scholar
23.Melki, J, Abdelhak, S, Sheth, P, Bachelot, MF, Burlet, P, Marcadet, A, Aicardi, J, Barois, A, Carriere, JP, Fardeau, M, Fontan, D, Ponsot, G, Billette, T, Angelini, C, Barbosa, C, Ferriere, G, Lanzi, G, Ottolini, A, Babton, MC, Cohen, D, Hanauer, A, Clerget-Darpoux, F, Lathrop, M, Munnich, A, Frezal, J (1990): Gene for chronic proximal spinal muscolar atrophies maps to chromosome 5q. Nature 344: 767–768.Google Scholar
24.Novelli, G, Capon, F, Tamisari, L, Grandi, E, Angelini, C, Guerrini, P, Dallapiccola, B (1995): Neonatal spinal muscular atrophy with diaphragmatic paralysis is unlinked to 5q11.2-q13. J Med Genet 32: 216–219.CrossRefGoogle Scholar
25.Novelli, G (1996): Spinal muscular atrophy: resources available on the world wide web. Mol Med Today 2: 369.Google Scholar
26.Osborne, LR, Soder, S, Shi, X-M, Pober, B, Costa, T, Scherer, SW, Tsui, L-C (1997): Hemizygous deletion of the syntaxin 1A gene in individuals with Williams syndrome. Am J Hum Genet 61: 449–452.CrossRefGoogle ScholarPubMed
27.Pizzuti, A, Amati, F, Calabrese, G, Mari, A, Colosimo, A, Silani, V, Giardino, L, Ratti, A, Penso, D, Calzà, L, Palka, G, Scarlato, G, Novelli, G, Dallapiccola, B (1996): cDNA characterization and chromosomal mapping of two human homologues of the Drosophila dishevelled polarity gene. Hum Mol Genet 5: 953–958.Google Scholar
28.Romeo, G, McKusik, VA (1994): Phenotypic diversity, allelic series and modifier genes. Nature Genet 7: 451–452.Google Scholar
29.Rubinsztein, DC, Leggo, J, Coles, R, Almqvist, E, Biancalana, V, Cassiman, JJ, Chotai, K, Connarty, M, Craufurd, D, Curtis, A, Curtis, D, Davidson, MJ, Differ, AM, Dode, C, Dodge, A, Frontali, M, Ranen, NG, Colin Stine, O, Sheer, M, Abbott, MH, Franz, ML, Graham, CA, Harper, PS, Hedreen, JC, Jackson, A, Kaplan, JC, Losekoot, M, McMillan, JC, Morrison, P, Trottier, Y, Novelletto, A, Simpson, SA, Theilmann, J, Whittaker, JL, Folstein, SE, Ross, CA, Hayden, MR (1996): Phenotypic characterization of individuals with 30-40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats. Am J Hum Genet 59: 16–222.Google Scholar
30.Ryan, AK, Goodship, JA, Wilson, DI, Philip, N, Levy, A, Seidel, H, Schulfenhauer, S, Oechsler, H, Belohradsky, , Prieur, M, Aurias, A, Raymond, FL, Clayton-Smith, J, Hatchwell, E, McKeown, C, Beemer, FA, Dallapiccola, B, Novelli, G, Hurst, JA, Ignatius, J, Green, AJ, Winter, RM, Brueton, L, Brøndum-Nielsen, K, Stewart, F, Van Essen, T, Patton, M, Paterson, J, Scambler, PJ (1997): Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet 34:798–804.Google Scholar
31.Speicher, MR, Gwyn Ballard, S, Ward, DC (1996): Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genet 12: 368–375.Google Scholar
32.Stern, CS (1997): The diagnosis of cystic fibrosis. N Engl J Med 336: 487–491Google Scholar
33.Sullivan, LS, Daiger, SP (1996): Inherited retinal degeneration: exceptional genetic and clinical heterogeneity. Mol Med Today: 380–386.Google Scholar
34.Surth, L, Robinson, A (1994): Genetic diagnosis: Present and prospects. Can Med Assoc J 150: 49–52.Google Scholar
35.The Cystic Fibrosis Genotype-Phenotype Consortium (1993): Correlation between genotype and phenotype in cystic fibrosis patients: analysis of seven common mutations. New Engl J Med 329: 1308–1313.Google Scholar
36.Wilkie, AOM (1997): Craniosynostosis: genes and mechanisms. Hum Mol Genet 6: 1647–1656.Google Scholar
37.Wolf, U (1997): Identical mutations and phenotipic variation. Hum Genet 100: 305–321.Google Scholar