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Chromosomal imbalance letter: Phenotypic consequences of combined deletion 8pter and duplication 15qter.

Sheth F, Andrieux J, Tewari S, Sheth H, Desai M, Kumari P, Nanavaty N, Sheth J - Mol Cytogenet (2013)

Bottom Line: Chromosomal imbalances have been identified as one of the major causes of mental retardation and/or malformation syndromes and they are observed in ~2-5% of the cases.The unique phenotypic presentation in our case may have resulted from either loss or gain of a series of contiguous genes which may have resulted in a direct phenotypic effect and/or caused a genetic regulatory disturbance.Double segmental aberrations may have conferred phenotypic variability, as in our case, making it difficult to predict the characteristics that evolved as a result of the global gene imbalance, caused by the concomitant deletion and duplication.

View Article: PubMed Central - HTML - PubMed

Affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.

ABSTRACT
Exact breakpoint determination by oligonucleotide array-CGH has improved the analysis of genotype-phenotype correlations in cases with chromosome aberrations allowing a more accurate definition of relevant genes, particularly their isolated or combined impact on the phenotype in an unbalanced state. Chromosomal imbalances have been identified as one of the major causes of mental retardation and/or malformation syndromes and they are observed in ~2-5% of the cases. Here we report a female child born to non-consanguineous parents and having multiple congenital anomalies such as atrial septal defect and multiple ventricular septal defects, convergent strabismus, micropthalmia, seizures and mental retardation, with her head circumference and stature normal for her age. Cytogenetic study suggested 46,XX,add(8)(p23). Further analysis by array-CGH using 44K oligonucleotide probe confirmed deletion on 8p23.3p23.1 of 7.1 Mb and duplication involving 15q23q26.3 of 30 Mb size leading to 46,XX,der(8)t(8;15)(p23.3;q23)pat.arr 8p23.3p23.1(191,530-7,303,237)x1,15q23q26.3(72,338,961-102,35,195)x3. The unique phenotypic presentation in our case may have resulted from either loss or gain of a series of contiguous genes which may have resulted in a direct phenotypic effect and/or caused a genetic regulatory disturbance. Double segmental aberrations may have conferred phenotypic variability, as in our case, making it difficult to predict the characteristics that evolved as a result of the global gene imbalance, caused by the concomitant deletion and duplication.

No MeSH data available.


Related in: MedlinePlus

Breakpoint characterization by 44K oligonucleotide array-CGH. a: 7.1 Mb deletion at 8p [arr 8p23.3p23.1(191,530-7,303,237)x1] and b: 30 Mb duplication at 15q [arr 15q23q26.3(chr15:72,338,961-102,351,195)x3].
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Figure 3: Breakpoint characterization by 44K oligonucleotide array-CGH. a: 7.1 Mb deletion at 8p [arr 8p23.3p23.1(191,530-7,303,237)x1] and b: 30 Mb duplication at 15q [arr 15q23q26.3(chr15:72,338,961-102,351,195)x3].

Mentions: Genomic DNA was extracted from peripheral blood lymphocytes using standard SDS-proteinase K extraction method [13]. Extracted genomic DNA concentration was determined with NanoDrop ND-1000 spectrophotometer (NanoDrop Technologies, Berlin, Germany). Evaluation of gene copy number was performed by 44k oligonucleotide array-Comparative Genomic Hybridization (aCGH) by following manufacturer's recommendations (Human Genome CGH microarray 44B kit, Agilent Technologies Inc., Santa Clara, CA, USA). Female genomic DNA (Promega Corporation, Madison, WI, USA) was used as a sex-matched reference, which was analyzed with the CGH-analysis software v3.4 (Agilent Technologies Inc., Santa Clara, CA, USA) by applying Z-score segmentation algorithm with a window size of 10 points to identify chromosome aberrations. Analysis was performed using 3-points filter and 0.2 variation which lead to confirmation of partial deletion 8p region of 7.1 Mb [arr cgh 8p23.3p23.1(191,530-7,303,237)(hg19-NCBI build37)x1] and partial 15q duplication of 30 Mb [arr cgh 15q23q26.3 (chr15:72,338,961-102,351,195)x3], i.e. 46,XX,der(8)t(8;15)(p23.3;q23)pat.arr 8p23.3p23.1(191,530-7,303,237)x1,15q23q26.3(72,338,961-102,351,195)x3 [Figure 3a,b].


Chromosomal imbalance letter: Phenotypic consequences of combined deletion 8pter and duplication 15qter.

Sheth F, Andrieux J, Tewari S, Sheth H, Desai M, Kumari P, Nanavaty N, Sheth J - Mol Cytogenet (2013)

Breakpoint characterization by 44K oligonucleotide array-CGH. a: 7.1 Mb deletion at 8p [arr 8p23.3p23.1(191,530-7,303,237)x1] and b: 30 Mb duplication at 15q [arr 15q23q26.3(chr15:72,338,961-102,351,195)x3].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750467&req=5

Figure 3: Breakpoint characterization by 44K oligonucleotide array-CGH. a: 7.1 Mb deletion at 8p [arr 8p23.3p23.1(191,530-7,303,237)x1] and b: 30 Mb duplication at 15q [arr 15q23q26.3(chr15:72,338,961-102,351,195)x3].
Mentions: Genomic DNA was extracted from peripheral blood lymphocytes using standard SDS-proteinase K extraction method [13]. Extracted genomic DNA concentration was determined with NanoDrop ND-1000 spectrophotometer (NanoDrop Technologies, Berlin, Germany). Evaluation of gene copy number was performed by 44k oligonucleotide array-Comparative Genomic Hybridization (aCGH) by following manufacturer's recommendations (Human Genome CGH microarray 44B kit, Agilent Technologies Inc., Santa Clara, CA, USA). Female genomic DNA (Promega Corporation, Madison, WI, USA) was used as a sex-matched reference, which was analyzed with the CGH-analysis software v3.4 (Agilent Technologies Inc., Santa Clara, CA, USA) by applying Z-score segmentation algorithm with a window size of 10 points to identify chromosome aberrations. Analysis was performed using 3-points filter and 0.2 variation which lead to confirmation of partial deletion 8p region of 7.1 Mb [arr cgh 8p23.3p23.1(191,530-7,303,237)(hg19-NCBI build37)x1] and partial 15q duplication of 30 Mb [arr cgh 15q23q26.3 (chr15:72,338,961-102,351,195)x3], i.e. 46,XX,der(8)t(8;15)(p23.3;q23)pat.arr 8p23.3p23.1(191,530-7,303,237)x1,15q23q26.3(72,338,961-102,351,195)x3 [Figure 3a,b].

Bottom Line: Chromosomal imbalances have been identified as one of the major causes of mental retardation and/or malformation syndromes and they are observed in ~2-5% of the cases.The unique phenotypic presentation in our case may have resulted from either loss or gain of a series of contiguous genes which may have resulted in a direct phenotypic effect and/or caused a genetic regulatory disturbance.Double segmental aberrations may have conferred phenotypic variability, as in our case, making it difficult to predict the characteristics that evolved as a result of the global gene imbalance, caused by the concomitant deletion and duplication.

View Article: PubMed Central - HTML - PubMed

Affiliation: FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, 380 015, India.

ABSTRACT
Exact breakpoint determination by oligonucleotide array-CGH has improved the analysis of genotype-phenotype correlations in cases with chromosome aberrations allowing a more accurate definition of relevant genes, particularly their isolated or combined impact on the phenotype in an unbalanced state. Chromosomal imbalances have been identified as one of the major causes of mental retardation and/or malformation syndromes and they are observed in ~2-5% of the cases. Here we report a female child born to non-consanguineous parents and having multiple congenital anomalies such as atrial septal defect and multiple ventricular septal defects, convergent strabismus, micropthalmia, seizures and mental retardation, with her head circumference and stature normal for her age. Cytogenetic study suggested 46,XX,add(8)(p23). Further analysis by array-CGH using 44K oligonucleotide probe confirmed deletion on 8p23.3p23.1 of 7.1 Mb and duplication involving 15q23q26.3 of 30 Mb size leading to 46,XX,der(8)t(8;15)(p23.3;q23)pat.arr 8p23.3p23.1(191,530-7,303,237)x1,15q23q26.3(72,338,961-102,35,195)x3. The unique phenotypic presentation in our case may have resulted from either loss or gain of a series of contiguous genes which may have resulted in a direct phenotypic effect and/or caused a genetic regulatory disturbance. Double segmental aberrations may have conferred phenotypic variability, as in our case, making it difficult to predict the characteristics that evolved as a result of the global gene imbalance, caused by the concomitant deletion and duplication.

No MeSH data available.


Related in: MedlinePlus