THE STUDY OF X CHROMOSOME INACTIVATION IN MENTAL RETARDATION: COMPARATIVE ANALYSIS OF MOLECULAR-CYTOGENETIC AND POLYMERASE CHAIN REACTION-BASED TECHNIQUES IN RETT SYNDROME
Iourov IY1, Vorsanova SG2,*, Villard L3, Kolotii AD2, Yurov YB1,*
*Corresponding Author: Professor Yuri B. Yurov and Professor Svetlana G. Vorsanova, Cytogenetic Labora¬tory National Center of Mental Health, Russian Academy of Medical Sciences, Zagorodnoe shosse 2, Moscow 113 152, Russia; Tel.: +7-095-952-89-90; Fax: +7-095-952-89-40; E-mail: y_yurov@hotmail.com; y_yurov@yahoo. com
page: 33

RESULTS

Thirty-three samples of peripheric blood lymphocytes, obtained from RTT girls and their parents, were analyzed by FISH with chromosome X-specific alphoid probe (pYAM10-40). In cells of eight RTT girls (24.2%) homol­ogous highly heteromorphic chromosomes X were found. In metaphase and interphase, one X chromosome had large or medium hybridization signals and the other chromo­some contained a very small hybridization signal (Fig. 1) This provided us with the possibility to accurately mark and differentiate the parental chromosome X. Chromo­somal preparations of an RTT girl’s parents were analyzed to determine the paternal or maternal origin of chromo­some X with alphoid DNA heteromorphism. Five girls had X chromosomes with small centromeric heteromorphism of paternal origin and three of maternal origin. The data of molecular-cytogenetic assays are shown in Table 1. Ac­cording to the molecular-cytogenetic study, one girl had random X-inactivation (55:45), four girls had moderate X-inactivation (from 63:37 to 74:26), and three girls had extremely skewed X-inactivation (more than 80:20).

We have performed a PCR-based methylation sensi­tive method for determining X-inactivation skewing on peripheric blood lymphocytes of the eight RTT girls. The results of HpaII digestion and PCR are presented in Fig. 2.

The data obtained and comparison of the two methods applied are presented in Table 1. There is good correlation of the results obtained by these two independent methods for X-inactivation analysis. Using molecucular-cyto­genetic and replication pattern analysis of active/inactive X chromosomes, we have found that active X chromo­somes have paternal origin in seven cases and maternal in one case of RTT girls (Table 1).

 

Table 1. Comparison of the results obtained by two X-inactivation assays (PCR-based and FISH methods) in eight patients with Rett syndrome.

 

 

Patient

 

MECP2

Mutation

 

PCR

Results

 

FISH

Results

 

Status of

X-Inactivation

 

Chromosome X

Active/Inactive Origin

 

1

 

T197M

 

51:49

 

55:45

 

random

 

maternal:paternal

 

2

 

R255X

 

76:24

 

74:26

 

moderately skewed

 

paternal:maternal

 

3

 

T158M

 

69:31

 

62:38

 

moderately skewed

 

paternal:maternal

 

4

 

no mutation

 

85:15

 

82:18

 

extremely skewed

 

paternal:maternal

 

5

 

R168M

 

90:10

 

91:9

 

extremely skewed

 

paternal:maternal

 

6

 

no mutation

 

60:40

 

64:36

 

moderately skewed

 

paternal:maternal

 

7

 

P388T

 

95:5

 

91:9

 

extremely skewed

 

paternal:maternal

 

8

 

no mutation

 

61:39

 

69:31

 

moderately skewed

 

paternal:maternal

 




Number 26
Number 26 VOL. 26(2), 2023 All in one
Number 26
VOL. 26(2), 2023
Number 26
VOL. 26, 2023 Supplement
Number 26
VOL. 26(1), 2023
Number 25
VOL. 25(2), 2022
Number 25
VOL. 25 (1), 2022
Number 24
VOL. 24(2), 2021
Number 24
VOL. 24(1), 2021
Number 23
VOL. 23(2), 2020
Number 22
VOL. 22(2), 2019
Number 22
VOL. 22(1), 2019
Number 22
VOL. 22, 2019 Supplement
Number 21
VOL. 21(2), 2018
Number 21
VOL. 21 (1), 2018
Number 21
VOL. 21, 2018 Supplement
Number 20
VOL. 20 (2), 2017
Number 20
VOL. 20 (1), 2017
Number 19
VOL. 19 (2), 2016
Number 19
VOL. 19 (1), 2016
Number 18
VOL. 18 (2), 2015
Number 18
VOL. 18 (1), 2015
Number 17
VOL. 17 (2), 2014
Number 17
VOL. 17 (1), 2014
Number 16
VOL. 16 (2), 2013
Number 16
VOL. 16 (1), 2013
Number 15
VOL. 15 (2), 2012
Number 15
VOL. 15, 2012 Supplement
Number 15
Vol. 15 (1), 2012
Number 14
14 - Vol. 14 (2), 2011
Number 14
The 9th Balkan Congress of Medical Genetics
Number 14
14 - Vol. 14 (1), 2011
Number 13
Vol. 13 (2), 2010
Number 13
Vol.13 (1), 2010
Number 12
Vol.12 (2), 2009
Number 12
Vol.12 (1), 2009
Number 11
Vol.11 (2),2008
Number 11
Vol.11 (1),2008
Number 10
Vol.10 (2), 2007
Number 10
10 (1),2007
Number 9
1&2, 2006
Number 9
3&4, 2006
Number 8
1&2, 2005
Number 8
3&4, 2004
Number 7
1&2, 2004
Number 6
3&4, 2003
Number 6
1&2, 2003
Number 5
3&4, 2002
Number 5
1&2, 2002
Number 4
Vol.3 (4), 2000
Number 4
Vol.2 (4), 1999
Number 4
Vol.1 (4), 1998
Number 4
3&4, 2001
Number 4
1&2, 2001
Number 3
Vol.3 (3), 2000
Number 3
Vol.2 (3), 1999
Number 3
Vol.1 (3), 1998
Number 2
Vol.3(2), 2000
Number 2
Vol.1 (2), 1998
Number 2
Vol.2 (2), 1999
Number 1
Vol.3 (1), 2000
Number 1
Vol.2 (1), 1999
Number 1
Vol.1 (1), 1998

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006