Background: Point mutations in SPG4, the gene encoding spastin, are a frequent cause of autosomal dominant hereditary spastic paraplegia (AD-HSP). However, standard methods for genetic analyses fail to detect exonic microdeletions.
Methods: 121 mutation-negative probands were screened for rearrangements in SPG4 by multiplex ligation-dependent probe amplification.
Results: 24 patients with 16 different heterozygotic exon deletions in SPG4 (20%) were identified, ranging from one exon to the whole coding sequence. Comparison with 78 patients with point mutations showed a similar clinical picture but an earlier age at onset.
Conclusions: Exon deletions in SPG4 are as frequent as point mutations, and SPG4 is responsible for 40% of AD-HSP.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2598038 | PMC |
http://dx.doi.org/10.1136/jmg.2006.046425 | DOI Listing |
Transl Psychiatry
January 2025
Department of Neuropsychiatry, Dongguk University, School of Medicine, Seoul, Republic of Korea.
Autism spectrum disorder (ASD) is linked to ion channel dysfunction, including chloride voltage-gated channel-4 (CLCN4). We generated Clcn4 knockout (KO) mice by deleting exon 5 of chromosome 7 in the C57BL/6 mice. Clcn4 KO exhibited reduced social interaction and increased repetitive behaviors assessed using three-chamber and marble burying tests.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy.
Anderson-Fabry (or Fabry) disease is a rare lysosomal storage disorder caused by a functional deficiency of the enzyme alpha-galactosidase A. The partial or total defect of this lysosomal enzyme, which is caused by variants in the gene, leads to the accumulation of glycosphingolipids, mainly globotriaosylceramide in the lysosomes of different cell types. The clinical presentation of Fabry disease is multisystemic and can vary depending on the specific genetic variants associated with the disease.
View Article and Find Full Text PDFGenes (Basel)
December 2024
The International Renal Research Institute of Vicenza (IRRIV) Foundation, ULSS 8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy.
: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is mainly characterized by renal involvement with progressive bilateral development of renal cysts and volumetric increase in the kidneys, causing a loss of renal function, chronic kidney disease (CKD), and kidney failure. The occurrence of mosaicism may modulate the clinical course of the disease. Mosaicism is characterized by a few cell populations with different genomes.
View Article and Find Full Text PDFCurr Oncol
January 2025
Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Douliu City 640, Taiwan.
Background: Afatinib and Osimertinib are first-line treatments for EGFR-mutated advanced non-small cell lung cancer (NSCLC), but their comparative efficacies and the patient groups that benefit the most remain unclear. This multicenter retrospective study evaluated the efficacy of first-line Afatinib and Osimertinib in NSCLC patients with EGFR 19del and no brain metastases at diagnosis.
Methods: The primary endpoints were time on treatment (ToT) and overall survival (OS).
Brain Dev
January 2025
Department of Pediatrics, Aichi Medical University School of Medicine, Nagakute, Japan.
Background: Most cases of spinal muscular atrophy (SMA) can be diagnosed by copy number analysis of survival motor neuron (SMN) 1. However, a small number of cases of SMA can only be diagnosed by sequencing analysis. We present a case of SMA diagnosed 7 years after the onset of symptoms.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!