Diagnosis of the Genomic Imprinting Diseases by the Usage of Conventional and Molecular Analyses

Ayşegül Öztürk Kaymak, Meral Yirmibeş Karaoğuz, Kıvılcım Gücüyener, Emriye Ferda Perçin

Abstract


Objective:Prader-Willi (PWS) and Angelman syndromes (AS) are genomic imprinting diseases with intellectual disability. In approximately 70 % of the cases, there is a cytogenetic deletion involving the chromosome 15q11-q13 inherited from patient’s father (in PWS) and from patient’s mother (in AS). In approximately 20-25% and 3-7% of the cases, there is an uniparental disomy (UPD) of chromosome 15 in PWS and AS patients, respectively. The mutation ratio in AS patients is approximately 10 %, while the ratio is two percent in PWS patients.

Methods: In the first step cytogenetic analyses were performed by using high resolution banding (HRB) for 20 patients who were selected by diagnostic criteria (11 pre-diagnosed with AS and 9 pre-diagnosed with PWS). Then, via Fluorescent in situ Hybridization (FISH) technique, SNRPN gene (small nuclear ribonucleoprotein polypeptide N gene) locus for PWS, D15S10 locus for AS were searched. Finally the uniparental disomy of chromosome 15 along with the mutation/deletion of imprinting center were examined.

Results: HRB and FISH analyses revealed no deletion except in one AS patient whose D15S10 region was found deleted via FISH technique. Mutation/deletion of imprinting center analyses in all of them were evaluated as normal.

Conclusion: As a result, by this project patients with PWS and AS, who were selected by the diagnostic criteria for each syndrome, were evaluated via conventional genetic and molecular genetics methods and they were offered with the efficient genetic counseling.


Keywords


Angelman syndrome, FISH, genomic imprinting,intellectual disability,Prader-Willi syndrome, uniparental disomy

References


Clayton-Smith J, Pembrey ME. Angelman syndrome. J Med Genet 1992;29:412-5.

Williams CA, Beaudet AL, Clyton-Smith J, Knoll JH, Kyllerman M, Laan LA, et al. Angelman Syndrome 2005. Am J Med Genet 2006;140A:413-8

Williams CA, Lossie A, Driscoll D, Philips Unit RC. Angelman syndrome: mimicking conditions and phenotypes. Am J Med Genet 2001;101:59-64.

Angelman H, 'Puppet children': a report of three cases. Dev Med Child Neurol 1965;7:681-8.

Cassidy SB, Discroll DJ. Prader Willi Syndrome. Eur J Hum Genet 2009;17:3-13

National Center of Biotechnology Information (NCBI)- Online Mendelian Inheritance in Man (OMIM) database

Ensemble Database

Yis U, Giray O, Kurul SH, Bora E, Ulgenalp A, Erçal D, et al. Long-standing fever and Angelman syndrome:Report of two cases. Journal of Paediatrics and Child Health. 2008;44: 308–10.

Stevenson DA, Anaya TM, Clayton-Smith J, Hall BD, Van Allen MI, Zori RT, et al. Unexpected death and critical illness in Prader–Willi syndrome: report of ten individuals. Am J Med Genet. 2004; 124: 158–64.

Ramsden SC, Clayton-Smith J, Birch R, Buiting K. Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes. BMC Medical Genetics 2010;11:70-81.


Full Text: PDF

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.