Publications by authors named "E Calpena"
Article Synopsis
- The study aimed to find the genetic cause of a rare skeletal Class II malocclusion with gingival hyperplasia in a family over four generations.
- SNP and exome sequencing identified regions on chromosomes 1, 17, and 19 but were inconclusive, leading to further genome sequencing that revealed a complex rearrangement on chromosome 17 involving portions from chromosome 1.
- This rearrangement is linked to misregulated genes KCNJ2/KCNJ16, suggesting a genetic basis for the observed phenotype and expanding the understanding of conditions associated with the KCNJ2-SOX9 locus.
Article Synopsis
- This study investigates the role of inversions—structural variants that involve the rearrangement of DNA—in genetic diseases, using data from 33,924 families involved in the 100,000 Genomes Project.
- Researchers identified 47 ultra-rare rearrangements, including de novo inversions, in genes linked to disease, with analyses correlating genetic findings to clinical outcomes in some cases, including a specific diagnosis for three family members.
- The findings suggest that while inversions are less common in genetic diseases compared to other structural variants, they can significantly contribute to the etiology in approximately 1 in 750 families with rare conditions.
Article Synopsis
- Whole genome sequencing (WGS) is being increasingly used to diagnose rare diseases, but traditional methods often have low diagnostic yields, typically 25-30%.
- In a study involving 122 rare disease patients and their relatives, a comprehensive bioinformatics approach led to a diagnostic yield of 35%, with 39% solved when including novel gene candidates.
- The study also identified several novel genes, expanded the phenotypic understanding of existing conditions, and resulted in critical changes to clinical diagnoses and treatments for some patients.
Article Synopsis
- The study investigates the role of the PRRX1 gene in craniosynostosis, focusing on how certain variants (missense and loss-of-function) affect craniofacial development, with previous research linking PRRX1 to preosteogenic cells in cranial sutures.
- Researchers used sequencing methods to identify rare variants in PRRX1 among patients suffering from craniosynostosis, discovering a total of 18 individuals with potential pathogenic variants and noting abnormal behavior of mutant proteins through immunofluorescence analyses.
- The findings highlight that PRRX1 plays a significant role in cranial suture development, and the presence of pathogenic variants is frequently inherited from non-affected relatives,
Craniosynostosis, the premature fusion of the cranial sutures, affects ~1 in 2000 children. Although many patients with a genetically determined cause harbor a variant in one of just seven genes or have a chromosomal abnormality, over 60 genes are known to be recurrently mutated, thus comprising a long tail of rarer diagnoses. Genome sequencing for the diagnosis of rare diseases is increasingly used in clinical settings, but analysis of the data is labor intensive and involves a trade-off between achieving high sensitivity or high precision.
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