Molecular versus classical cytogenetics - evaluation of 20 Prader-Willi syndrome patients

• Autorzy: Stankiewicz P , Lebiocka J , Szpecht-Potocka A , Bocian E , Stanczak H , Obersztyn E , Mazurczak T
• Języki publikacji: EN

Abstrakty

EN

Prader-Willi syndrome (PWS) is a developmental disorder caused by a deficiency of paternal contribution of the chromosome region 15q11.2-q13 arising from differently sized deletions, maternal disomy, or rarely imprinting mutations. We have analyzed 20 PWS patients using combined cytogenetic high resolution technique (HRT), fluorescence in situ hybridization (FISH) and molecular studies to identify parental origin (uniparental disomy) or molecular defect (deletion) of the Prader-Willi region. Lack of a paternal copy of 15q11.2-q13 resulting from its deletion was found in 16 patients. Using high resolution GTG banding on prometaphase chromosomes, deletion in the 15q11.2-q13 region was detected in only 8 patients. Application of FISH with different sets of PWS specific unique sequence probes (D15S11, SNRPN, D15S10, GABRß3) revealed microdeletions in 12 patients. In 12 out of 20 cases FISH confirmed HRT studies, while in 8 cases inconsistent results were obtained. No discrepancies between results of FISH and molecular studies were found, although the latter had a higher sensitivity. We conclude that FISH appears to be a rapid and reliable method of microdeletion identification and should be performed as a method of choice in cytogenetic diagnosis of Prader-Willi syndrome.

Słowa kluczowe

EN

chromosomal deletion; in situ; patient; hybridization; fluorescence; cytogenetics; chromosome region; Prader-Willi syndrome

• Wydawca: -
• Czasopismo: Journal of Applied Genetics
• Rocznik: 1997
• Tom: 38
• Numer: 2
• Opis fizyczny: p.217-226,fig.

Twórcy

autor

Stankiewicz P

• Department of Genetics, National Research Institute of Mother and Child, Kasprzaka 17A, 01-211 Warsaw, Poland

autor

Lebiocka J

• Department of Genetics, National Research Institute of Mother and Child, Kasprzaka 17A, 01-211 Warsaw, Poland

autor

Szpecht-Potocka A

• Department of Genetics, National Research Institute of Mother and Child, Kasprzaka 17A, 01-211 Warsaw, Poland

autor

Bocian E

• Department of Genetics, National Research Institute of Mother and Child, Kasprzaka 17A, 01-211 Warsaw, Poland

autor

Stanczak H

• Department of Genetics, National Research Institute of Mother and Child, Kasprzaka 17A, 01-211 Warsaw, Poland

autor

Obersztyn E

• Department of Genetics, National Research Institute of Mother and Child, Kasprzaka 17A, 01-211 Warsaw, Poland

autor

Mazurczak T

• Department of Genetics, National Research Institute of Mother and Child, Kasprzaka 17A, 01-211 Warsaw, Poland

Bibliografia

• ASHG/ACMG REPORT (1996). Diagnostic testing for Prader-Willi and Angelman syndromes: Report of the ASHG/ACMG test and technology transfer committee. Am. J. Hum. Genet. 58: 1085-1088.
• Bettio D., Rizzi N., Giardino D., Grugni G., Briscioli V., Selicorni A., Carnevale F., Larizza L. (1995). FISH analysis in Prader-Willi and Angelman syndrome patients. Am. J. Med. Gen. 56: 224-228.
• Bocian E., Stankiewicz P., Stańczak H., Obersztyn E., Mazurczak T., Mazurczak T. (1996). Identification of three different chromosomal additions by chromosome painting using fluorescence in situ hybridization (FISH) technique. J. Appl. Genet. 37: 197-204.
• Buiting K., Dittrich B., Robinson W.P., Guitart M., Abeliovich D., Lerer I., Horsthemke B. (1994). Detection of aberrant DNA methylation in unique Prader-Willi syndrome patients and its diagnostic implications. Hum. Mol. Genet. 3: 863-895.
• Buiting K., Saitoh S., Gross S., Dittrich B., Schwarz S., Nichols R.D., Horsthemke B. (1995). Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting center on human chromosome 15. Nature Genet. 9: 395-400.
• Burke L.W., Wiley J.E., Glenn C.C., Driscoll D.J., Loud K.M., Smith A.J.W., Kushnick T. (1996). Familial cryptic translocation resulting in Angelman syndrome: Implications for imprinting or location of the Angclman gene? Am. J. Hum. Genet. 58: 777-784.
• Butler M.G. (1990). Review: Prader-Willi syndrome - current understanding of cause and diagnosis. Am. J. Med. Genet. 35: 316-322.
• Butler M.G. (1994). Are specific short arm variants or heteromorphism over-represented in the chromosome 15 deletion in Angelman or Prader-Willi syndrome patients? Am. J. Med. Genet. 50: 42-44.
• Butler M.G. (1995). High resolution chromosome analysis and fluorescence in situ hybridization in patients referred for Prader-Willi or Angelman syndrome. Am. J. Med. Genet. 56: 420-422.
• Craig J.M., Bickmore W.A. (1994). The distribution of CpG islands in mammalian chromosomes. Nature Genet. 7: 376-382.
• Delach J.A., Rosengren S.S., Kaplan L., Greenstein R., Cassidy S.B., Benn P.A. (1994). Comparison of high resolution chromosome banding and fluorescence in situ hybridization (FISH) for the laboratory evaluation of Prader-Willi syndrome and Angelman syndrome. Am. J. Med. Gen. 52: 85-91.
• Erdel M., Schuffenhauer S., Buchholz B., Barth-Witte U., Köchl S., Uermann B., Duba H.C., Utermann G. (1996). Routine screening for microdeletions by FISH in 77 patients suspected of having Prader-Willi or Angelman syndromes using YAC clone 273A2 (D15S10). Hum. Genet. 97: 784-793.
• Friedrich U., Caprani M., Niebuhr E., Therkelsen A.J., Jørgensen A.L. (1996). Extreme variant of the short arm of chromosome 15. Hum. Genet. 97: 710-713.
• Holm V.A., Casidy S.B., Butler M.G., Hanchat J.M., Greenswag L.R., Whitman B.Y., Greenberg F. (1993). Prader-Willi syndrome: Consensus diagnostic criteria. Pediatrics 1: 398-402.
• Imaizumi K., Takada F., Kuroki Y., Naritomi K., Hamabe J., Nhkawa N. (1990). Cytogenetic and molecular study of the Angelman syndrome. Am. J. Med. Gen. 35: 314-318.
• Jauch A., Robson L., Smith A. (1995). Investigations with fluorescence in situ hybridization (FISH) demonstrate loss of the telomeres on the reciprocal chromosome in three unbalanced translocations involving chromosome 15 in the Prader-Willi and Angelman syndromes. Hum. Genet. 96: 345-349.
• Knoll J.H.M., Wagstaff J., Lalande M. (1993). Cytogenetic and molecular studies in the Prader-Willi and Angclman syndromes: An overview. Am. J. Med. Genet. 46: 2-6.
• Knoll J.H.M., Cheng S.D., Lalande M. (1994). Allele specificity of DNA replication timing in the Angelman/Pradcr-Willi syndrome imprinted chromosomal region. Nature Genet. 6: 31-46.
• Kuwano A., Mutirangura A., Dittrich B., Buiting K., Horsthemke B., Saitoh S., Nhkawa N., Ledbetter S.A., Greenberg F., Chinault A.C., Ledbetter D. (1992). Molecular dissection of the Prader-Willi/Angelman syndrome region (15q11- 13) by YAC cloning and FISH analysis. Hum. Mol. Genet. 1: 417-425.
• Magenis R.E., Toth-Fejel S., Allen L.J., Black M., Brown M.G., Budden S., Cohen R., Friedman J.M., Kalousek J.M., Zonana J., Lacy D., LaFranchi S., Lahr M., MacFarlane J., Williams C.P.S. (1990). Comparison of the 15q deletions in Prader-Willi and Angelman syndromes: Specific regions, extent of deletions, parental origin, and clinical consequences. Am. J. Med. Genet. 35: 333-349.
• Mutirangura A., Jayakumar A., Sutcliffe J.S., Nakao M., McKinney M.J., Buiting K., Horsthemke B., Beaudet A.L., Chinault A.C., Ledbetter D.H. (1993). A complete Yac contig of the Prader-Willi/Angelman chromosome region (15q11-q13) and refined localization of the SNRPN gene. Genomics 18: 546-552.
• Özaelik T., Leff S., Robinson W., Donlon T., Lalande M., Sanjines E., Schinzel A., Francke U. (1992). Small nuclear ribonuclcoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. Nature Genet. 2: 265-269.
• Rao V.V.N.G., Roops H., Carpenter N.J. (1995). Diagnosis of microdeletion syndromes: High-resolution chromosome analysis versus fluorescence in situ hybridization. Am. J. Med. Sci. 309(4): 208-212.
• Rivera H., Zuffardi O., Gargantini L. (1990). Nonreciprocal and jumping translocations of 15ql→qter in Prader-Willi syndrome. Am. J. Med. Genet. 37: 311-317.
• Robinson W.P., Lalande M. (1995). Sex-specific meiotic recombination in the Prader-Willi/Angelman syndrome imprinted region. Hum. Mol. Genet. 4: 801- 806.
• Schinzel A. A., Brecevic L., Barnasconi F., Binkert F., Berthet F., Wuilloud A., Robinson W.P. (1994). Intrachromosomal triplication of 15q11-13. J. Med. Genet. 31:798-803.
• Sun Y., Nicholls R.D., Butler M.G., Saitoh S., Hainline B.E., Palmer C.G. (1996). Breakage in the SNRPN locus in a balanced 46, XY,t(15;19) Prader-Willi syndrome patient. Nature Genet. 5: 517-524.
• Szpecht-Potocka A., Bal J., Mazurczak T. (1994). Molecular analysis in the clinical diagnosis of Prader-Willi and Angelman syndromes. Pediatr. Pol. 69, 10: 817-823.
• Toth-Fejel S., Magenis R.E., Leff S., Brown M.G., Comegys B., Ławce H., Berry T., Kesner D., Webb M.J., Olson S. (1995). Prenatal diagnosis of chromosome 15 abnormalities in the Prader-Willi/Angelman syndrome region by traditional and molecular cytogenetics. Am. J. Med. Genet. 55: 444-452.
• Wevrick R., Kerns J.A., Francke U. (1994). Identification of a novel paternally expressed gene in the Prader-Willi syndrome region. Hum. Mol. Genet. 3: 1877-1882.
• Woodage T., Deng Z-М., Prasad M., Smart R., Lindeman R., Christan S.L., Ledbetter D.H., Robson L., Smith A., Trent R.J. (1994). A variety of genetic mechanisms are associated with the Prader-Willi syndrome. Am. J. Med. Genet. 54: 219-226.
• YunisJ.J. (1976). High resolution of human chromosomes. Science 191: 1268-1270.
• Zackowski J.L., Nicholls R.D., Gray B.A., Bent-Williams a., Gottlieb W., Harris PJ., Waters M.F., Driscoll D.J., Zori R.T., Williams C.A. (1993). Cytogenetic and molecular analysis in Angelman syndrome. Am. J. Med. Genet. 46: 7-11.