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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

Metaphase showing signals of both BAC clones RP11-95F11 and RP11-100A1 spanning 15q25.3 to 15q26.3 region on two normal #15 and on derivative #8p [thin arrow]. Whereas, clone RP11-139L10 covering 8p23.3 is seen only on normal #8p [broad arrow].
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Figure 4: Metaphase showing signals of both BAC clones RP11-95F11 and RP11-100A1 spanning 15q25.3 to 15q26.3 region on two normal #15 and on derivative #8p [thin arrow]. Whereas, clone RP11-139L10 covering 8p23.3 is seen only on normal #8p [broad arrow].

Mentions: FISH analysis was performed using BAC clones RP11-139L10 covering 8p23 → pter, RP11-95F11 and RP11-100A1 spanning 15q23 → qter. Nick Translation Kit (Vysis, Abbott Molecular, USA) was used for labeling. The two clones - RP11-95F11 and RP11-100A1 were labeled with Spectrum Orange and Spectrum Green respectively whereas, third BAC clone was labeled using both fluorochromes in 1:1 ratio labeling. FISH signals were observed using Olympus BX-51 microscope (Olympus, Germany) and pseudo-coloring was carried out using Adobe Photoshop [Figure 4].


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)

Metaphase showing signals of both BAC clones RP11-95F11 and RP11-100A1 spanning 15q25.3 to 15q26.3 region on two normal #15 and on derivative #8p [thin arrow]. Whereas, clone RP11-139L10 covering 8p23.3 is seen only on normal #8p [broad arrow].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Metaphase showing signals of both BAC clones RP11-95F11 and RP11-100A1 spanning 15q25.3 to 15q26.3 region on two normal #15 and on derivative #8p [thin arrow]. Whereas, clone RP11-139L10 covering 8p23.3 is seen only on normal #8p [broad arrow].
Mentions: FISH analysis was performed using BAC clones RP11-139L10 covering 8p23 → pter, RP11-95F11 and RP11-100A1 spanning 15q23 → qter. Nick Translation Kit (Vysis, Abbott Molecular, USA) was used for labeling. The two clones - RP11-95F11 and RP11-100A1 were labeled with Spectrum Orange and Spectrum Green respectively whereas, third BAC clone was labeled using both fluorochromes in 1:1 ratio labeling. FISH signals were observed using Olympus BX-51 microscope (Olympus, Germany) and pseudo-coloring was carried out using Adobe Photoshop [Figure 4].

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