Assuntos
Algoritmos , Cromossomos Humanos X , Feto/metabolismo , Monossomia/diagnóstico , Mosaicismo , Diagnóstico Pré-Natal , Adulto , Aberrações Cromossômicas/estatística & dados numéricos , Cromossomos Humanos X/genética , Reações Falso-Positivas , Feminino , Feto/patologia , Humanos , Testes para Triagem do Soro Materno/métodos , Testes para Triagem do Soro Materno/estatística & dados numéricos , Monossomia/genética , Mosaicismo/estatística & dados numéricos , Mães/estatística & dados numéricos , Gravidez , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/estatística & dados numéricos , Síndrome de Turner/diagnóstico , Síndrome de Turner/epidemiologiaRESUMO
Objective: Noninvasive prenatal testing (NIPT) for fetal aneuploidies has been widely adopted in developed countries. Despite the sharp decrease in the cost of massively parallel sequencing, the technical know-how and skilled personnel are still one of the major limiting factors for applying this technology to NIPT in low-income settings. Here, we present the establishment and validation of our NIPT procedure called triSure for detection of fetal aneuploidies. Methods: We established the triSure algorithm based on the difference in proportion of fetal and maternal fragments from the target chromosome to all chromosomes. Our algorithm was validated using a published data set and an in-house data set obtained from high-risk pregnant women in Vietnam who have undergone amniotic testing. Several other aneuploidy calling methods were also applied to the same data set to benchmark triSure performance. Results: The triSure algorithm showed similar accuracy to size-based method when comparing them using published data set. Using our in-house data set from 130 consecutive samples, we showed that triSure correctly identified the most samples (overall sensitivity and specificity of 0.983 and 0.986, respectively) compared to other methods tested including count-based, sized-based, RAPIDR and NIPTeR. Conclusions: We have demonstrated that our triSure NIPT procedure can be applied to pregnant women in low-income settings such as Vietnam, providing low-risk screening option to reduce the need for invasive diagnostic tests.
Assuntos
Aneuploidia , Ácidos Nucleicos Livres/análise , Teste Pré-Natal não Invasivo/métodos , Adulto , Algoritmos , Estudos de Casos e Controles , Ácidos Nucleicos Livres/sangue , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 21/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pessoa de Meia-Idade , Gravidez , Análise de Sequência de DNA/métodos , Trissomia/diagnóstico , Trissomia/genética , Vietnã , Adulto JovemRESUMO
BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary syndrome characterised by the development of hundreds to thousands of adenomatous colonic polyps during the second decade of life. FAP is caused by germ line mutations in the adenomatous polyposis coli (APC) gene located on chromosome 5q21-22. CASE PRESENTATION: A 36-year-old female was presented with 100-1000 adenomatous colonic polyps, typical of classic FAP symptoms. Genetic testing using massively parallel sequencing identified a 5-bp deletion (c.3927_3931delAAAGA) which causes frameshift (p.Glu1309Aspfs) and creates a premature stop codon, resulting in the replacement of the last 1535 amino acids of APC by five incorrect amino acids. Two of the proband's four siblings also exhibited classic FAP symptoms and carried the same 5-bp heterozygous deletion in the APC gene. One of the proband's two nephews also tested positive for this mutation but has not been examined by endoscopy due to his young age. CONCLUSIONS: We reported here for the first time the use of massively parallel sequencing (MPS)-based genetic testing to identify a germline mutation within a three-generation Vietnamese family. This mutation is most likely responsible for the development of FAP.
Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Mutação da Fase de Leitura , Heterozigoto , Polipose Adenomatosa do Colo/etnologia , Polipose Adenomatosa do Colo/cirurgia , Adulto , Povo Asiático , Pré-Escolar , Cromossomos Humanos Par 5/química , Colectomia/métodos , Feminino , Expressão Gênica , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Irmãos , VietnãRESUMO
Rearrangements involving chromosome region at 12p13 are common abnormalities in hematological malignancies, including myeloid and lymphoid types. ETV6 gene is usually involved in the 12p13 region. ETV6 rearrangements are more often observed in acute lymphoblastic leukemia than in acute myeloid leukemia (AML), where ETV6 gene deletions are more common than rearrangements. Here, we report an AML case with the recurrent t(10; 12) (q24; p13) as the sole abnormality. Fluorescence in situ hybridization with mapping back to metaphases confirmed that the ETV6 gene splits, and rearranges with a locus at 10q24. In review of the literature, this is the first report of AML case with the novel abnormality as the sole change. Complete laboratory findings from bone marrow examination, flow cytometry analysis, cytogenetic studies, molecular analysis, and clinical features are also described in the report.
