Project description:The ataxia telangiectasia mutant (ATM) protein is a sensor and signal transducer that amplifies and communicates signals of DNA damage further to the mediators of cell cycle arrest, apoptosis, and senescence (p16, p19, p21, BAX etc.) which is modified by the strength of the cellular stress. They are able to act as recognition and signaling proteins because of their kinase activity. Classic ataxia telangiectasia is associated with homozygous mutations of the ATM gene, the complete absence of its kinase activity and/or deleterious ATM gene mutations such as truncation/nonsense mutations, loss of function mutation, non-conservative substitutions, frameshift, and deletions. On the other hand, variant ataxia-telangiectasia (A-T) is associated with the presence of residual kinase activity. We report a six-year-old male patient who presented to us with abnormal neck movements as his initial complaint. ATM gene analysis showed a rare pathogenic variant of the ATM gene. The variant was a homozygous nonsense mutation in exon 2 of the ATM gene that resulted in the formation of a stop codon and premature truncation of the protein at codon 23 in exon 2 (p.Arg23Ter). In conclusion, we report a case of an unusual presentation of classic A-T. We should pursue a long-term follow-up and maintain a low threshold for performing pedigree analysis and genetic testing in pediatric patients with movement disorders. In resource-limited settings where kinase enzyme assays are not universally available to patients, web-based mutation prediction tools may be beneficial to predict the deleterious effects of the mutation.

| S-EPMC9697739 | biostudies-literature

Pearls & Oy-sters: ophthalmic artery malperfusion in aortic dissection with common carotid artery involvement.

Project description: Not available

| S-EPMC4336075 | biostudies-literature

Pearls & Oy-sters: A rare presentation of chronic intracranial hypertension with concurrent deafness and blindness.

Project description: Not available

| S-EPMC4955278 | biostudies-literature

Pearls & Oy-sters: CNS lymphoma in a patient with relapsing-remitting multiple sclerosis treated with interferon.

Project description: Not available

| S-EPMC5664305 | biostudies-literature

Ataxia telangiectasia presenting as dopa-responsive cervical dystonia.

Project description:ObjectiveTo identify the cause of cervical dopa-responsive dystonia (DRD) in a Muslim Indian family inherited in an apparently autosomal recessive fashion, as previously described in this journal.MethodsPrevious testing for mutations in the genes known to cause DRD (GCH1, TH, and SPR) had been negative. Whole exome sequencing was performed on all 3 affected individuals for whom DNA was available to identify potentially pathogenic shared variants. Genotyping data obtained for all 3 affected individuals using the OmniExpress single nucleotide polymorphism chip (Illumina, San Diego, CA) were used to perform linkage analysis, autozygosity mapping, and copy number variation analysis. Sanger sequencing was used to confirm all variants.ResultsAfter filtering of the variants, exome sequencing revealed 2 genes harboring potentially pathogenic compound heterozygous variants (ATM and LRRC16A). Of these, the variants in ATM segregated perfectly with the cervical DRD. Both mutations detected in ATM have been shown to be pathogenic, and α-fetoprotein, a marker of ataxia telangiectasia, was increased in all affected individuals.ConclusionBiallelic mutations in ATM can cause DRD, and mutations in this gene should be considered in the differential diagnosis of unexplained DRD, particularly if the dystonia is cervical and if there is a recessive family history. ATM has previously been reported to cause isolated cervical dystonia, but never, to our knowledge, DRD. Individuals with dystonia related to ataxia telangiectasia may benefit from a trial of levodopa.

| S-EPMC3795596 | biostudies-literature

Dystonia in Patients With Spinocerebellar Ataxia Type 2.

Project description:Dystonia has been described in various genetically proven spinocerebellar ataxias (SCAs), most often in SCA3, SCA17, and SCA2 patients. In this report, we describe different types of dystonia observed in 5 of our 11 SCA2 patients. All our patients had cranial and/or cervical dystonia with focal or segmental distribution. Except for 1 case with isolated cervical dystonia, all other patients had lower cranial affection of variable severity. Although it is difficult to describe ataxia-dystonia syndrome that would be highly characteristic for SCA2, we suggest that occurrence of dystonia in a patient with slowly evolving cerebellar disease should, besides SCA3 and SCA17, also suggest SCA2 testing. In patients with lower cranial dystonia, especially jaw and tongue dystonia, SCA2 should be considered during the diagnostic workup.

| S-EPMC6353333 | biostudies-literature

Jaw-Opening Oromandibular Dystonia Associated With Spinocerebellar Ataxia Type 2.

Project description: Not available

| S-EPMC6183243 | biostudies-literature