Dataset Information

Clinical application of targeted long read sequencing in prenatal beta-thalassemia testing and genetic counseling.

ABSTRACT:

Background

Beta thalassemia, related to HBB mutation and associated with elevated hemoglobin A2 (HbA2), is an important genetic hemoglobinopathy with high incidences of disease and carrier rates in Singapore. Carrier screening is essential to facilitate prenatal counseling and testing. However, when individuals with elevated HbA2 do not have an identifiable HBB disease-associated variant, there is ambiguity on risk to their offspring.

Methods

We describe a case report of a proband with elevated HbA2, no identifiable HBB disease-associated variant, whose partner was a beta thalassemia carrier. Through clinical HBB gene sequencing, multiplex ligation-dependent probe amplification (MLPA) analysis, as well as targeted Nanopore long read sequencing of selected genes, we performed a complete analysis of HBB including the promoter region, 5'UTR and coding gene sequence, as well as evaluation for potential modifier variants and other rare structural variants.

Results

This process identified that the proband was heterozygous for KLF1:c.544T>C (p.Phe182Leu), a potential functional polymorphism previously known to be associated with benign elevated HbA2 levels. The presence of disease variants in the HBB locus was excluded.

Conclusion

This finding provided clarity and enabled family planning for the proband and her family.

SUBMITTER: Chin HL

PROVIDER: S-EPMC10767580 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Clinical application of targeted long read sequencing in prenatal beta-thalassemia testing and genetic counseling.

Chin Hui-Lin HL Benton Miles C MC Yang Lin L Poon Kok Siong KS Tan Karen M L KML Jamuar Saumya S SS Foo Roger R Law Hai Yang HY Goh Denise Li-Meng DL Chong Samuel S SS de Sessions Paola Florez PF

Molecular genetics & genomic medicine 20230923 1

<h4>Background</h4>Beta thalassemia, related to HBB mutation and associated with elevated hemoglobin A2 (HbA2), is an important genetic hemoglobinopathy with high incidences of disease and carrier rates in Singapore. Carrier screening is essential to facilitate prenatal counseling and testing. However, when individuals with elevated HbA2 do not have an identifiable HBB disease-associated variant, there is ambiguity on risk to their offspring.<h4>Methods</h4>We describe a case report of a proband ...[more]

PMID: 37740604

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Dataset Information

Clinical application of targeted long read sequencing in prenatal beta-thalassemia testing and genetic counseling.

Background

Methods

Results

Conclusion

Publications

Clinical application of targeted long read sequencing in prenatal beta-thalassemia testing and genetic counseling.

Similar Datasets

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