Dataset Information

Genetic origin of ?0-thalassemia (SEA deletion) in Southeast Asian populations and application to accurate prenatal diagnosis of Hb Bart's hydrops fetalis syndrome.

ABSTRACT: ?0-thalassemia of SEA deletion (-SEA) is common among Southeast Asian and Chinese. Using haplotype and phylogenetic analyses, we examined the origin of this defect in Southeast Asian populations. Study was done on both normal and ?0-thalassemia alleles in 3 ethnic groups including 96 Thai, 52 Laotian and 21 Cambodian. Five SNPs encompassing the (-SEA) including (rs3760053 T>G), (rs1211375 A>C), (rs3918352 A>G), (rs1203974 A>G) and (rs11248914 C>T) were examined using high-resolution melting assays. It was found that 94.0% of Thai, 100% of Laotian and 100% of Cambodian ?0-thalassemia alleles were linked to the same haplotype: the haplotype H4 (AAGC), representing an Asian specific origin. An G allele of the (rs3760053) was found to be in strong linkage disequilibrium with the ?0-thalassemia allele in these populations. A multiplex PCR assay was developed to detect simultaneously the (-SEA) allele and genotyping of a linked (rs3760053) to improve accuracy of prenatal diagnosis of ?0-thalassemia. Application of this multiplex PCR assay for routine prenatal diagnosis of ?0-thalassemia in 12 families revealed a 100% concordant result with conventional gap-PCR assay. Therefore, a single genetic origin is responsible for the spread and high prevalence of the (-SEA) in the region. The multiplex PCR assay developed should provide a double-check PCR system for more accurate diagnosis and allow the monitoring of possible maternal contamination at prenatal diagnosis of this important genetic disorder.

SUBMITTER: Jomoui W

PROVIDER: S-EPMC5584512 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Genetic origin of α0-thalassemia (SEA deletion) in Southeast Asian populations and application to accurate prenatal diagnosis of Hb Bart's hydrops fetalis syndrome.

Jomoui Wittaya W Fucharoen Goonnapa G Sanchaisuriya Kanokwan K Charoenwijitkul Patnaree P Maneesarn Jitpanu J Xu Xiangmin X Fucharoen Supan S

Journal of human genetics 20170406 8

α0-thalassemia of SEA deletion (-SEA) is common among Southeast Asian and Chinese. Using haplotype and phylogenetic analyses, we examined the origin of this defect in Southeast Asian populations. Study was done on both normal and α0-thalassemia alleles in 3 ethnic groups including 96 Thai, 52 Laotian and 21 Cambodian. Five SNPs encompassing the (-SEA) including (rs3760053 T>G), (rs1211375 A>C), (rs3918352 A>G), (rs1203974 A>G) and (rs11248914 C>T) were ...[more]

PMID: 28381876

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Project description:BackgroundThe cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear.MethodsWe evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited.ResultsIn 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases.ConclusionsIn this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases. (Funded by the UCSF Center for Maternal-Fetal Precision Medicine and others; ClinicalTrials.gov number, NCT03412760.).

Dataset Information

Genetic origin of ?0-thalassemia (SEA deletion) in Southeast Asian populations and application to accurate prenatal diagnosis of Hb Bart's hydrops fetalis syndrome.

Publications

Genetic origin of α<sup>0</sup>-thalassemia (SEA deletion) in Southeast Asian populations and application to accurate prenatal diagnosis of Hb Bart's hydrops fetalis syndrome.

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