Limits...
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

Partial karyotype of the father showing breakpoints on both derivative chromosomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3750467&req=5

Figure 2: Partial karyotype of the father showing breakpoints on both derivative chromosomes.

Mentions: After obtaining institutional ethical committee approval and informed written consent form, metaphase chromosome preparations were obtained from PHA stimulated lymphocyte cultures according to the standard procedure with slight modifications [12]. Chromosome analysis was carried out by GTG-banding at 550-band level according to ISCN 2013 nomenclature in both patient and parents (50 metaphases, each). Patient’s karyotype pattern showed additional genetic material on the short arm of #8p i.e.46,XX,add(8)(p23). Parental chromosomal investigation revealed that the father was a carrier of a balanced translocation 46,XY,t(8;15)(p23;q23) [Figure 2]. This suggests that the child had inherited der(8) from the father thus leading to an unbalanced genetic makeup.


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)

Partial karyotype of the father showing breakpoints on both derivative chromosomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Partial karyotype of the father showing breakpoints on both derivative chromosomes.
Mentions: After obtaining institutional ethical committee approval and informed written consent form, metaphase chromosome preparations were obtained from PHA stimulated lymphocyte cultures according to the standard procedure with slight modifications [12]. Chromosome analysis was carried out by GTG-banding at 550-band level according to ISCN 2013 nomenclature in both patient and parents (50 metaphases, each). Patient’s karyotype pattern showed additional genetic material on the short arm of #8p i.e.46,XX,add(8)(p23). Parental chromosomal investigation revealed that the father was a carrier of a balanced translocation 46,XY,t(8;15)(p23;q23) [Figure 2]. This suggests that the child had inherited der(8) from the father thus leading to an unbalanced genetic makeup.

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