UNASSIGNED: Patent foramen ovale (PFO) has a genetic predisposition and is closely associated with cryptogenic stroke (CS), migraine, decompression sickness, and hypoxemia. Identifying PFO-related mutant genes through whole-exome sequencing (WES) can help in the early recognition of cardiovascular genetic risk factors, guide timely clinical intervention, and reduce the occurrence of cardiovascular events.
UNASSIGNED: We analyzed mutant genes from ClinVar and OMIM databases. WES was performed on 25 PFO patients from Zhejiang Provincial Hospital of Chinese Medicine. Pathogenicity of variants was evaluated using American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology. (AMP) guidelines.
UNASSIGNED: In ClinVar (4 Feb 2023), 113 coding gene mutations were found, including 83 associated with PFO. From OMIM (18 Apr 2023), 184 gene mutations were analyzed, with 110 mutant coding genes. WES identified pathogenic mutations in two of 25 PFO patients (8%). LDLR, SDHC, and NKX2-5 genes were linked to PFO and primarily involved in myocardial tissue function. NKX2-5 may play a crucial role in PFO development, interacting with NOTCH1, GATA4, MYH6, SCN5A signaling pathways regulating cardiomyocyte characteristics.
UNASSIGNED: We identified pathogenic mutations in LDLR, SDHC, and NKX2-5 genes, implying their role in PFO development. Functional enrichment analysis revealed NKX2-5\'s interaction with signaling pathways regulating cardiomyocyte function. These findings enhance our understanding of PFO\'s genetic basis, suggesting potential therapeutic targets for future research.

In this large-sample study, we demonstrated that osteogenesis imperfecta (OI) significantly impaired the quality of life (QoL) in children. Moderate/severe OI patients had worse QoL scores than patients with mild OI. Furthermore, the QoL for OI patients was correlated with the presence of pathogenic gene mutations.
BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary disease characterized by multiple fragility fractures and progressive skeletal deformities. No detailed investigations about the quality of life (QoL) have been carried out in a large sample of patients with OI. We evaluated the QoL and its influencing factors in a large and well-characterized OI cohort.
METHODS: We used a validated questionnaire of PedsQL 4.0 to evaluate the health-related quality of life (HRQoL) of children and adolescents with OI. We compared HRQoL among patients with OI types I, III, and IV. The relationship between HRQoL and pathogenic mutations in candidate OI genes was investigated. We also evaluated the influencing factors of HRQoL in OI patients.
RESULTS: A total of 138 children with OI and 138 healthy controls were enrolled in this study. The HRQoL scores of OI patients were 64.4 ± 30.0, 71.9 ± 22.2, 75.7 ± 24.8, 63.7 ± 24.5, and 68.9 ± 22.0 in physical, emotional, social, school functioning, and total score, respectively, which were significantly lower than those of healthy children (86.5 ± 12.7, 83.3 ± 16.0, 92.1 ± 11.8, 87.5 ± 11.8, and 87.3 ± 10.7, all p < 0.01). Moderate and severe OI (type III/IV) patients had poorer HRQoL scores than patients with mild OI (type I). Gene mutations inducing qualitative defects in type I collagen led to worse HRQoL scores than those with quantitative defects in type I collagen, except in emotional functioning. The total HRQoL score was positively correlated with family income, lumbar, and femoral bone mineral density (BMD) Z-scores and negatively correlated with disease severity and fracture frequency.
CONCLUSIONS: HRQoL was significantly impaired in OI patients, and patients with more severe OI had poorer HRQoL scores. For the first time, we found that children with qualitative defects in type I collagen had poorer HRQoL scores than those with quantitative defects in type I collagen.

In this study, the role of known Parkinson\'s disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.