Limits...
Compound heterozygous β(+) β(0) mutation of HBB gene leading to β-thalassemia major in a Gujarati family - A case study.

Chaudhary S, Dhawan D, Bagali PG, S Chaudhary P, Chaudhary A, Singh S, Vudathala S - Mol Genet Metab Rep (2016)

Bottom Line: After analysis, the father was found to be heterozygous for HBBc.92G > C (Codon 30 (G > C)) mutation which is β(0) type and the mother was heterozygous for HBBc.92 + 5G > C (IVS I-5 (G > C)) mutation which is β(+) type.When amniotic fluid sample was analyzed for β-globin gene (HBB), we found the occurrence of heterozygous allelic pattern for aforesaid mutations.Prenatal diagnosis helps the parents to know the thalassemic status of the fetus and enables an early decision on the pregnancy.

View Article: PubMed Central - PubMed

Affiliation: Medical Genetics and Diagnostics Division, Xcelris Labs Ltd., Old Premchand Nagar Road, Opp. Satyagrah Chhavani, Bodakdev, Ahmedabad 380015, Gujarat, India.

ABSTRACT
β-Thalassemia is a genetic disease characterized by reduced or non-functionality of β-globin gene expression, which is caused due to a number of variations and indels (insertions and deletions). In this case study, we have reported a rare occurrence of compound heterozygosity of two different variants, namely, HBBc.92G > C and HBBc.92 + 5G > C in maternal amniotic fluid sample. Prenatal β-thalassemia mutation detection in fetal DNA was carried out using nucleotide sequencing method. After analysis, the father was found to be heterozygous for HBBc.92G > C (Codon 30 (G > C)) mutation which is β(0) type and the mother was heterozygous for HBBc.92 + 5G > C (IVS I-5 (G > C)) mutation which is β(+) type. When amniotic fluid sample was analyzed for β-globin gene (HBB), we found the occurrence of heterozygous allelic pattern for aforesaid mutations. This compound heterozygous state of fetus sample was considered as β(+)/β(0) category of β thalassemia which was clinically and genotypically interpreted as β-thalassemia major. Regular blood transfusions are required for the survival of thalassemia major patients hence prenatal diagnosis is imperative for timely patient management. Prenatal diagnosis helps the parents to know the thalassemic status of the fetus and enables an early decision on the pregnancy. In the present study, we have identified compound heterozygosity for β-thalassemia in the fetus which portrays the importance of prenatal screening.

No MeSH data available.


Related in: MedlinePlus

Electropherogram of bidirectional sequencing analysis demonstrated heterozygous mutation [c.92 + 5G > C (IVS I-5 G > C)] and [c.92G > C (codon30 G > C)] in amniotic fluid sample.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4834677&req=5

f0005: Electropherogram of bidirectional sequencing analysis demonstrated heterozygous mutation [c.92 + 5G > C (IVS I-5 G > C)] and [c.92G > C (codon30 G > C)] in amniotic fluid sample.

Mentions: β-Thalassemia mutations were detected using nucleotide sequencing technology (ABI3730) on trio samples (parental blood and maternal amniotic fluid samples). DNA was subjected to quality check followed by target specific PCR amplification and Sanger sequencing. Our analysis confirmed that the father was heterozygous for HBBc.92G > C(Codon 30 (G > C)), which is β0 type of mutation and the mother was found to be heterozygous for HBBc.92 + 5G > C (IVS I-5 (G > C)), which is β+ type of mutation. When the chromogram of amniotic fluid sample was analyzed, we found the occurrence of HBBc.92G > C and HBBc.92 + 5G > C mutations in the compound heterozygous state (Fig. 1). This genotype pattern belonged to β+β0 category and causes clinically and phenotypically severe health conditions similar to β-thalassemia major. Our results corroborated the test results from hemoglobin electrophoresis method for parent samples.


Compound heterozygous β(+) β(0) mutation of HBB gene leading to β-thalassemia major in a Gujarati family - A case study.

Chaudhary S, Dhawan D, Bagali PG, S Chaudhary P, Chaudhary A, Singh S, Vudathala S - Mol Genet Metab Rep (2016)

Electropherogram of bidirectional sequencing analysis demonstrated heterozygous mutation [c.92 + 5G > C (IVS I-5 G > C)] and [c.92G > C (codon30 G > C)] in amniotic fluid sample.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834677&req=5

f0005: Electropherogram of bidirectional sequencing analysis demonstrated heterozygous mutation [c.92 + 5G > C (IVS I-5 G > C)] and [c.92G > C (codon30 G > C)] in amniotic fluid sample.
Mentions: β-Thalassemia mutations were detected using nucleotide sequencing technology (ABI3730) on trio samples (parental blood and maternal amniotic fluid samples). DNA was subjected to quality check followed by target specific PCR amplification and Sanger sequencing. Our analysis confirmed that the father was heterozygous for HBBc.92G > C(Codon 30 (G > C)), which is β0 type of mutation and the mother was found to be heterozygous for HBBc.92 + 5G > C (IVS I-5 (G > C)), which is β+ type of mutation. When the chromogram of amniotic fluid sample was analyzed, we found the occurrence of HBBc.92G > C and HBBc.92 + 5G > C mutations in the compound heterozygous state (Fig. 1). This genotype pattern belonged to β+β0 category and causes clinically and phenotypically severe health conditions similar to β-thalassemia major. Our results corroborated the test results from hemoglobin electrophoresis method for parent samples.

Bottom Line: After analysis, the father was found to be heterozygous for HBBc.92G > C (Codon 30 (G > C)) mutation which is β(0) type and the mother was heterozygous for HBBc.92 + 5G > C (IVS I-5 (G > C)) mutation which is β(+) type.When amniotic fluid sample was analyzed for β-globin gene (HBB), we found the occurrence of heterozygous allelic pattern for aforesaid mutations.Prenatal diagnosis helps the parents to know the thalassemic status of the fetus and enables an early decision on the pregnancy.

View Article: PubMed Central - PubMed

Affiliation: Medical Genetics and Diagnostics Division, Xcelris Labs Ltd., Old Premchand Nagar Road, Opp. Satyagrah Chhavani, Bodakdev, Ahmedabad 380015, Gujarat, India.

ABSTRACT
β-Thalassemia is a genetic disease characterized by reduced or non-functionality of β-globin gene expression, which is caused due to a number of variations and indels (insertions and deletions). In this case study, we have reported a rare occurrence of compound heterozygosity of two different variants, namely, HBBc.92G > C and HBBc.92 + 5G > C in maternal amniotic fluid sample. Prenatal β-thalassemia mutation detection in fetal DNA was carried out using nucleotide sequencing method. After analysis, the father was found to be heterozygous for HBBc.92G > C (Codon 30 (G > C)) mutation which is β(0) type and the mother was heterozygous for HBBc.92 + 5G > C (IVS I-5 (G > C)) mutation which is β(+) type. When amniotic fluid sample was analyzed for β-globin gene (HBB), we found the occurrence of heterozygous allelic pattern for aforesaid mutations. This compound heterozygous state of fetus sample was considered as β(+)/β(0) category of β thalassemia which was clinically and genotypically interpreted as β-thalassemia major. Regular blood transfusions are required for the survival of thalassemia major patients hence prenatal diagnosis is imperative for timely patient management. Prenatal diagnosis helps the parents to know the thalassemic status of the fetus and enables an early decision on the pregnancy. In the present study, we have identified compound heterozygosity for β-thalassemia in the fetus which portrays the importance of prenatal screening.

No MeSH data available.


Related in: MedlinePlus