After an impressively successful application as a research instrument, whole-exome sequencing (WES) now enters the clinical practice due to its high diagnostic, time, and economic efficiency. WES is the diagnostic method of choice for symptoms that may be due to many different monogenic causes. Neurological indications include movement disorders, especially in cases of early symptom onset, familial clustering and complex manifestation. Starting from a blood sample, enrichment and sequencing of the exome enable the examination of all coding DNA regions for point mutations and small insertions/deletions. The identification of variants as the cause of a disease requires a professional evaluation pipeline, variant prioritization schemes and variant classification databases. Whereas many variants can be reliably classified as pathogenic or benign, variants of unclear significance (VUS) remain a challenge for the clinical evaluation and necessitate a periodic reanalysis of WES data. As a genetic examination WES requires adequate patient informed consent which in particular should address possible secondary findings as well as data security. A positive molecular result ends diagnostic odysseys, enables accurate genetic counseling and can point to targeted preventive measures and treatment. A WES significantly contributes to the understanding of the genetic architecture and pathophysiology of neurological diseases, enriching and enabling precision medicine.
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http://dx.doi.org/10.1007/s00115-018-0667-1 | DOI Listing |
Front Oncol
January 2025
Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Introduction: Primary cilia play an important role in the development of cancer by regulating signaling pathways. Several studies have demonstrated that women with mutations have, on average, 50% fewer ciliated cells compared with general women. However, the role of tubal cilia loss in the development of epithelial ovarian cancer (EOC) remains unclear.
View Article and Find Full Text PDFJ Neural Transm (Vienna)
January 2025
Section of Adult Neurology, Department of Internal Medicine, Chong Hua Hospital, Fuente, Cebu, Philippines.
Joubert Syndrome (JS) is a congenital cerebellar ataxia typically inherited in an autosomal recessive pattern, although rare X-linked inheritance can occur. It is characterized by hypotonia evolving into ataxia, global developmental delay, oculomotor apraxia, breathing dysregulation, and multiorgan involvement. To date, there are 40 causative genes implicated in JS, all of which encode proteins of the primary cilium.
View Article and Find Full Text PDFInt Med Case Rep J
January 2025
Vincent van Gogh Centre of Excellence for Neuropsychiatry, Venray, The Netherlands.
Introduction: Levocarnitine is essential for brain functioning and fatty acid metabolism and stems largely from dietary sources. The Epsilon-Trimethyllysine Hydroxylase () gene encodes the enzyme N-Trimethyllysine hydroxylase (TMLH) which catalyses the first step in the biosynthesis of carnitine. Lack of TMLH enzyme activity is associated with developmental delay and autistic behaviours described as X-linked recessive autism, type 6 (OMIM#300872).
View Article and Find Full Text PDFFront Genet
January 2025
Genetics and Precision Medical Center, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Introduction: Mucopolysaccharidosis type VI (MPSVI), an autosomal recessive lysosomal storage disorder caused by pathogenic variants in gene. Usually, whole exome sequencing (WES) can identify these variants, and if WES failed to detect causative variants, whole-genome sequencing (WGS) may be considered to investigate deep intronic variations and structural alterations in patients.
Methods: Whole-exome sequencing (WES) and whole genome sequencing (WGS) were performed in a Chinese family having a boy with suspected diagnosis of MPS with macrocephaly, coarse facial features, broad forehead, thick lips, frontal bossing, craniosynostosis, blue spots, frequent upper respiratory infections, inguinal hernia, and dysostosis multiplex.
Clin Proteomics
January 2025
Division of Breast Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
Integrating functional proteomics and next-generation sequencing (NGS) offers a comprehensive approach to unraveling the molecular intricacies of breast cancer. This study investigates the functional interplay between genomic alterations and protein expression in Taiwanese breast cancer patients. By analyzing 61 breast cancer samples using tandem mass tag (TMT) labeling and mass spectrometry, coupled with whole-exome sequencing (WES) or targeted sequencing, we identified key genetic mutations and their impact on protein expression.
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