7 research outputs found
Table9_Prenatal genetic diagnosis associated with fetal ventricular septal defect: an assessment based on chromosomal microarray analysis and exome sequencing.DOCX
Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling.Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses.Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes.Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities.</p
Table7_Prenatal genetic diagnosis associated with fetal ventricular septal defect: an assessment based on chromosomal microarray analysis and exome sequencing.DOCX
Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling.Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses.Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes.Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities.</p
Table8_Prenatal genetic diagnosis associated with fetal ventricular septal defect: an assessment based on chromosomal microarray analysis and exome sequencing.DOCX
Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling.Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses.Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes.Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities.</p
State Interaction Linear Response Time-Dependent Density Functional Theory with Perturbative Spin–Orbit Coupling: Benchmark and Perspectives
Spin–orbit coupling (SOC) is an important driving
force
in photochemistry. In this work, we develop a perturbative spin–orbit
coupling method within the linear response time-dependent density
function theory framework (TDDFT-SO). A full state interaction scheme,
including singlet–triplet and triplet–triplet coupling,
is introduced to describe not only the coupling between the ground
and excited states, but also between excited states with all couplings
between spin microstates. In addition, expressions to compute spectral
oscillator strengths are presented. Scalar relativity is included
variationally using the second-order Douglas-Kroll-Hess Hamiltonian,
and the TDDFT-SO method is validated against variational SOC relativistic
methods for atomic, diatomic, and transition metal complexes to determine
the range of applicability and potential limitations. To demonstrate
the robustness of TDDFT-SO for large-scale chemical systems, the UV–Vis
spectrum of Au25(SR)18– is computed and compared to experiment.
Perspectives on the limitation, accuracy, and capability of perturbative
TDDFT-SO are presented via analyses of benchmark calculations. Additionally,
an open-source Python software package (PyTDDFT-SO) is developed and released to interface with the Gaussian 16 quantum
chemistry software package to perform this calculation
State Interaction Linear Response Time-Dependent Density Functional Theory with Perturbative Spin–Orbit Coupling: Benchmark and Perspectives
Spin–orbit coupling (SOC) is an important driving
force
in photochemistry. In this work, we develop a perturbative spin–orbit
coupling method within the linear response time-dependent density
function theory framework (TDDFT-SO). A full state interaction scheme,
including singlet–triplet and triplet–triplet coupling,
is introduced to describe not only the coupling between the ground
and excited states, but also between excited states with all couplings
between spin microstates. In addition, expressions to compute spectral
oscillator strengths are presented. Scalar relativity is included
variationally using the second-order Douglas-Kroll-Hess Hamiltonian,
and the TDDFT-SO method is validated against variational SOC relativistic
methods for atomic, diatomic, and transition metal complexes to determine
the range of applicability and potential limitations. To demonstrate
the robustness of TDDFT-SO for large-scale chemical systems, the UV–Vis
spectrum of Au25(SR)18– is computed and compared to experiment.
Perspectives on the limitation, accuracy, and capability of perturbative
TDDFT-SO are presented via analyses of benchmark calculations. Additionally,
an open-source Python software package (PyTDDFT-SO) is developed and released to interface with the Gaussian 16 quantum
chemistry software package to perform this calculation
Comparison of Variational and Perturbative Spin–Orbit Coupling within Two-Component CASSCF
The
modeling of spin–orbit coupling (SOC) remains a challenge
in computational chemistry due to the high computational cost. With
the rising popularity of spin-driven processes and f-block metals
in chemistry and materials science, it is incumbent on the community
to develop accurate multiconfigurational SOC methods that scale to
large systems and understand the limits of different treatments of
SOC. Herein, we introduce an implementation of perturbative SOC in
scalar-relativistic two-component CASSCF (srX2C-CASSCF-SO). Perspectives
on the limitations and accuracy of srX2C-CASSCF-SO are presented via
benchmark calculations
Table2_Prenatal diagnosis of 21 fetuses with balanced chromosomal abnormalities (BCAs) using whole-genome sequencing.DOCX
Balanced chromosomal abnormalities (BCAs) are the most common chromosomal abnormalities and the frequency of congenital abnormalities is approximately twice as high in newborns with a de novo BCA, but a prenatal diagnosis based on BCAs is subject to evaluation. To detect translocation breakpoints and conduct a prenatal diagnosis, we performed whole-genome sequencing (WGS) in 21 subjects who were found BCAs, 19 balanced chromosome translocations and two inversions, in prenatal screening. In 16 BCAs on non-N-masked regions (non-NMRs), WGS detected 13 (81.2%, 13/16) BCAs, including all the inversions. All the breakpoints of 12 (12/14) cases of sufficient DNA were confirmed by Sanger sequencing. In 13 interrupted genes, CACNA1E (in case 12) and STARD7 (in case 17) are known causative and PDCL was found in subject (case 11) with situs inversus for the first time. Case 12 with abnormal ultrasound reached a definitive genetic diagnosis of CACNA1E-disease, while STARD7 exon deletion has never been found causative in patients. WGS provides the possibility of prenatal diagnosis in fetuses with BCAs, and its clinical significance also lies in providing data for postnatal diagnosis.</p