1p36 Microdeletion Syndrome: Diagnostic Problems and the Use of Molecular Cytogenetic Technologies for the Solution

Partial 1p36 monosomy is one of the most frequent microdeletion syndromes. However, the diagnosis appears to be hindered due to the exceptional clinical diversity. Here, we present a comparative analysis of cytogenetic and molecular cytogenetic methods employed for testing of this chromosomal aberration in children with mental retardation and congenital malformations. Application of cytogenetic techniques allowed us to reveal terminal 1p36 deletions in 0.1% of cases (2 of 1874). Molecular cytogenetic analysis performed by conventional comparative genomic hybridization (CGH) uncovered 1p36 deletions in 1.3% cases (2 of 150). Using highresolution microarray CGH (array CGH) we found microdeletions in 2.4 % (3 of 125) cases. Detected chromosomal rearrangements were confirmed by a fluorescent in situ hybridization. Array CGH allowed us to characterize the loss of genetic material in microdeletions with 1-10 kbp resolution. It was concluded that molecular diagnosis of 1p36 microdeletion syndrome requires the application of such innovative molecular cytogenetic technologies as array CGH. Our study enabled to estimate for the first time the frequency of 1p36 microdeletion syndrome among children with mental retardation and congenital malformations in the Russian Federation, which appeared to be about 2%.

1. Heterochromatic regions of human chromosomes: medical and biological aspects / S.G. Vorsanova, I.Y. Iourov, I.V. Soloviev, Y.B. Yurov. – M., 2008. – 300 р.

2. Iourov I.Y. Genomic and chromosomal disorders of the central nervous system: molecular and cytogenetic aspects / I.Y. Iourov, S.G. Vorsanova, Y.B. Yurov. – M., 2014. – 384 р.

3. Battaglia A. Del 1p36 syndrome: a newly emerging clinical entity / A. Battaglia // Brain Dev. – 2005. – Vol. 27, №5. – P. 358 - 361.

4. Gajecka M. Monosomy 1p36 deletion syndrome / M. Gajecka, K.L. Mackay, L.G. Shaffer // Am. J. Med. Genet. C. Semin. Med. Genet. – 2007. – 145C, №4. – P. 346 - 356.

5. Recurrent interstitial 1p36 deletions: Evidence for germline mosaicism and complex rearrangement breakpoints / M. Gajecka, S.C. Saitta, A.J. Gentles [et al.] // Am. J. Med. Genet. A. – 2010. – Vol. 152A, №12. – P. 3074 - 3083.

6. Iourov I.Y. Molecular cytogenetics and cytogenomics of brain diseases / I.Y. Iourov, S.G. Vorsanova, Y.B. Yurov // Curr. Genomics. – 2008. – Vol. 9, №7. – P.452 - 465.

7. First case of del(1)(p36.2p33) in a fetus delivered stillborn / I.Y. Iourov, S.G. Vorsanova, E.A. Kirillova, Y.B. Yurov // Prenat. Diagn. – 2006. – Vol. 26, №11. – P.1092 - 1093.

8. Molecular karyotyping by array CGH in a Russian cohort of children with intellectual disability, autism, epilepsy and congenital anomalies / I.Y. Iourov, S.G. Vorsanova, O.S. Kurinnaia [et al.] // Mol. Cytogenet. – 2012. – Vol. 5. – 46.