Yulan Lu | Search PubMed

PubMed2026

TargetQC: A targeted quality control framework for clinical genomic testing.

Reliable genetic testing depends on accurate assessment of sequencing quality in clinically relevant genomic regions that directly influence variant interpretation. We developed TargetQC, a flexible quality control framework that supports user-defined gene sets, coverage thresholds, and variant sets for evaluating sequencing performance across exome sequencing (ES) and genome sequencing (GS) platforms. TargetQC assesses exon and gene coverage, identifies regions meeting predefined coverage thresholds, evaluates variant detection accuracy, and measures sequencing quality at pathogenic variant sites. We applied TargetQC to the reference sample NA12878 and 665 clinical samples across five ES platforms and one GS platform. ES-VendorB and ES-VendorE achieved the most complete coverage of OMIM coding regions in NA12878, whereas ES-VendorD and ES-VendorE showed the highest coverage compliance in clinical samples. ES-VendorB and GS demonstrated the highest variant detection accuracy. TargetQC provides a practical framework for benchmarking sequencing performance and informing platform selection in clinical genomics.

exome sequencing↗

PubMed2025

Deep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature review.

BACKGROUND: Chromosome 17p13.3 is a region of genomic instability associated with different neurodevelopmental diseases. The malformation spectrum of 17p13.3 microdeletions ranges from an isolated lissencephaly sequence to Miller-Dieker syndrome, while 17p13.3 microduplications result in autism, learning disabilities, microcephaly and other brain malformations. This study aims to provide a more comprehensive delineation of the clinical and genetic characteristics associated with 17p13.3 alterations. METHODS: We retrospectively analyzed the next-generation sequencing (NGS) data of more than 40 thousand patients from January 2016 to December 2021 and identified 38 pediatric patients with copy-number variations (CNVs) or single-nucleotide variations (SNVs) in 17p13.3 region. Published patients with CNVs in the 17p13.3 region were also collected and we performed a Chi-square test to compare the phenotype spectrum of microdeletions and microduplications. RESULTS: Among the 27 CNV patients, 20 patients with microdeletions and 7 patients with microduplications were found. PAFAH1B1 was the most frequently deleted gene and CRK was the most frequently duplicated gene. Affected genes in 11 SNV patients included PAFAH1B1 and PRPF8. Developmental delay was the most common abnormality detected in the 38 patients (29/38, 76.3%). Of note, Case 10 presented omphalocele and Case 23 presented scoliosis, webbed neck and bone cyst, all of which were unusual variant phenotypes in this region. The Chi-square test revealed that epilepsy, lissencephaly and short stature were statistically significant with microdeletions, while behavioral abnormalities and hand and foot abnormalities were significant with microduplications (p < 0.01). CONCLUSIONS: While PAFAH1B1, YWHAE and CRK are associated with major phenotypes of 17p13.3, RTN4RL1 may be involved in white matter changes and HIC1 might contribute to the occurrence of omphalocele. This study provided a comprehensive understanding of genetic information and phenotype spectrum of the 17p13.3 region.

Humans↗