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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

HBB gene structure denoting both the studied mutation.
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f0015: HBB gene structure denoting both the studied mutation.

Mentions: HBBc.92 + 5G > C mutation is the most prevalent variation worldwide and many documented cases of compound heterozygous mutations like deletion-inversion Gγ(Aγδβ)0, HBB: c. 93-2A > C and -42C > G with HBBc.92 + 5G > C are available in literature [13], [14], [15]. HBB gene is having two intronic and three exonic regions (Fig. 3). The variants detected in parents are located in the first intron and first exon of HBB gene. In HBBc.92 + 5G > C variant, 5th base of intron 1 changes from G to C which disrupts the normal splicing leading to the first exon being continued past the 5′ splice site and instead splice at a cryptic splice site that is few nucleotides past 5′ end causing β+ type mutation. The HBBc.92 G > C variant is located in the coding region of HBB gene. These two mutations HBBc.92G > C and HBBc.92 + 5G > C are located at the distance of 5 base pairs on HBB gene and probability of occurrence of both mutations in the same couple is very low. Segregation of compound heterozygosity has occurred twice in this family.


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)

HBB gene structure denoting both the studied mutation.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0015: HBB gene structure denoting both the studied mutation.
Mentions: HBBc.92 + 5G > C mutation is the most prevalent variation worldwide and many documented cases of compound heterozygous mutations like deletion-inversion Gγ(Aγδβ)0, HBB: c. 93-2A > C and -42C > G with HBBc.92 + 5G > C are available in literature [13], [14], [15]. HBB gene is having two intronic and three exonic regions (Fig. 3). The variants detected in parents are located in the first intron and first exon of HBB gene. In HBBc.92 + 5G > C variant, 5th base of intron 1 changes from G to C which disrupts the normal splicing leading to the first exon being continued past the 5′ splice site and instead splice at a cryptic splice site that is few nucleotides past 5′ end causing β+ type mutation. The HBBc.92 G > C variant is located in the coding region of HBB gene. These two mutations HBBc.92G > C and HBBc.92 + 5G > C are located at the distance of 5 base pairs on HBB gene and probability of occurrence of both mutations in the same couple is very low. Segregation of compound heterozygosity has occurred twice in this family.

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