RESUMO
Congenital heart disease (CHD), comprising structural or functional abnormalities present at birth, is the most common birth defect in humans. Reduced expression of connexin40 (Cx40) has been found in association with atrial fibrillation, and deletion of Cx40 in a mouse model causes various structural heart abnormalities in 18% of heterozygotes. We screened 505 unrelated CHD cases for deletions or duplications of the Cx40 gene (GJA5) by real-time quantitative PCR, in order to determine whether altered copy number of this gene may be associated with a cardiac phenotype in humans. Dosage of Cx40 flanking genes (ACPL1 and Cx50 gene, GJA8) was determined by real-time PCR for all apparent positive cases. In total, 3 cases were found to carry deletions on chromosome 1q21.1 spanning ACPL1, Cx40, and Cx50 genes. Absence of heterozygosity was observed in all 3 index cases over a 1.5- to 3-Mb region. Samples from the parents of two cases were obtained, and microsatellites across 1q21.1 were genotyped. One of the apparently unaffected parents was found to carry this deletion. All 3 index cases presented with obstruction of the aortic arch as the common structural cardiac malformation, and had no consistent dysmorphic features. Genotyping of 520 unrelated normal controls for this deletion was negative. We hypothesize that this 1q21.1 multigene deletion is associated with a range of cardiac defects, with anomalies of the aortic arch being a particular feature.
Assuntos
Aorta Torácica/anormalidades , Cromossomos Humanos Par 1/genética , Conexinas/genética , Deleção de Genes , Cardiopatias Congênitas/genética , Fosfatase Ácida/genética , Adolescente , Adulto , Animais , Aorta Torácica/embriologia , Criança , Pré-Escolar , Cromossomos Humanos Par 1/ultraestrutura , Sistemas Computacionais , Conexinas/deficiência , Proteínas do Olho/genética , Feminino , Cardiopatias Congênitas/embriologia , Humanos , Lactente , Recém-Nascido , Perda de Heterozigosidade , Masculino , Camundongos , Repetições de Microssatélites , Modelos Animais , Penetrância , Reação em Cadeia da Polimerase , Proteína alfa-5 de Junções ComunicantesRESUMO
BACKGROUND/AIM: To evaluate and compare the performance of the recently released Aneufast™ v2 (MolgentixSL) and QST*RplusV2 commercial assays (Gen-Probe), both designed for the quantitative fluorescent-polymerase chain reaction (PCR) detection of the common aneuploidies during pregnancy. METHODS: A series of 160 consecutive fetal samples referred for rapid aneuploidy detection testing and an additional 25 samples enriched for the presence of an abnormality were selected for comparison. RESULTS: To confidently rule out a chromosome abnormality, a second round of short tandem repeat typing was required for 14.1% (26) and 9.7% (18) of the specimens analyzed with Aneufast v2 and QST*RplusV2, respectively. Reflex testing was required for 7.6% (14) and 5.9% (11) of the specimens analyzed with respective assays to confidently rule out an autosomal trisomy. For the sex chromosomes, the difference in the amount of follow-up testing is greater between the assays, as a result of the inclusion in the initial PCR of the TAF9L paralogous marker in the QST*RplusV2 assay. CONCLUSIONS: Overall, both assays performed similarly in the detection of aneuploidies. In this sample set, the QST*RplusV2 kit required less frequent reflex testing, which translates into shorter turnaround time and cost savings. The incorporation of the TAF9L paralogous sequence in the initial PCR is advantageous for diagnostic use.