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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

Clinical presentation of the proband at 8 years of age.
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Figure 1: Clinical presentation of the proband at 8 years of age.

Mentions: At the age of 4 years, the head circumference was 47 cm (10th percentile), height 94.5 cm (15th percentile) and weight 14.5 kg (25th percentile) [11]. The prominent dysmorphic features were ptosis, downward slanted palpebral fissure, microphthalmia, left convergent strabismus, wide nasal base, long philtrum, open mouth, low set ears, short neck, micrognathia, puffy cheeks, short fingers, bilateral 1st incurved finger and absence of thenar eminence [Figure 1]. Developmental delay was evident from the first year as social smile was absent even at 6 months. She learnt sitting at 10 months and walking at 20 months. Speech was absent and her developmental quotient at presentation was of a 2 year old child. She had 3 attacks of partial seizures during the first 20 months and was kept on carbamazepine 150 mg/day and sodium valproate 100 mg/day till she was 5 years old. Since then, she has been free of epileptic symptoms. Sequential complete hemogram was suggestive of chronic iron deficiency anemia with hemoglobin levels of 8–8.5 gm%. 2D echocardiograph again at 3 years showed multiple small muscular VSDs and a single ASD of 4.2 × 7.0 mm.


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)

Clinical presentation of the proband at 8 years of age.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Clinical presentation of the proband at 8 years of age.
Mentions: At the age of 4 years, the head circumference was 47 cm (10th percentile), height 94.5 cm (15th percentile) and weight 14.5 kg (25th percentile) [11]. The prominent dysmorphic features were ptosis, downward slanted palpebral fissure, microphthalmia, left convergent strabismus, wide nasal base, long philtrum, open mouth, low set ears, short neck, micrognathia, puffy cheeks, short fingers, bilateral 1st incurved finger and absence of thenar eminence [Figure 1]. Developmental delay was evident from the first year as social smile was absent even at 6 months. She learnt sitting at 10 months and walking at 20 months. Speech was absent and her developmental quotient at presentation was of a 2 year old child. She had 3 attacks of partial seizures during the first 20 months and was kept on carbamazepine 150 mg/day and sodium valproate 100 mg/day till she was 5 years old. Since then, she has been free of epileptic symptoms. Sequential complete hemogram was suggestive of chronic iron deficiency anemia with hemoglobin levels of 8–8.5 gm%. 2D echocardiograph again at 3 years showed multiple small muscular VSDs and a single ASD of 4.2 × 7.0 mm.

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