ATXN2 and its neighbouring gene SH2B3 are associated with increased ALS risk in the Turkish population

Expansions of the polyglutamine (polyQ) domain (≥34) in Ataxin-2 (ATXN2) are the primary cause of spinocerebellar ataxia type 2 (SCA2). Recent studies reported that intermediate-length (27–33) expansions increase the risk of Amyotrophic Lateral Sclerosis (ALS) in 1–4% of cases in diverse populations. This study investigates the Turkish population with respect to ALS risk, genotyping 158 sporadic, 78 familial patients and 420 neurologically healthy controls. We re-assessed the effect of ATXN2 expansions and extended the analysis for the first time to cover the ATXN2 locus with 18 Single Nucleotide Polymorphisms (SNPs) and their haplotypes. In accordance with other studies, our results confirmed that 31–32 polyQ repeats in the ATXN2 gene are associated with risk of developing ALS in 1.7% of the Turkish ALS cohort (p = 0.0172). Additionally, a significant association of a 136 kb haplotype block across the ATXN2 and SH2B3 genes was found in 19.4% of a subset of our ALS cohort and in 10.1% of the controls (p = 0.0057, OR: 2.23). ATXN2 and SH2B3 encode proteins that both interact with growth receptor tyrosine kinases. Our novel observations suggest that genotyping of SNPs at this locus may be useful for the study of ALS risk in a high percentage of individuals and that ATXN2 and SH2B3 variants may interact in modulating the disease pathway

History of Myasthenia Gravis Revisited

The first description of myasthenia gravis (MG) was given by Thomas Willis in 1672. MG was the focus of attention after mid-nineteenth century and a great amount of information has been accumulated in a span of 150 years. The aim of this review is to convey this information according to a particular systematic and to briefly relate the experience of Istanbul University. MG history was examined in four periods: 1868-1930, 1930-1960, 1960-1990, and 1990-2020. In the first period (7868-7930), all the clinical characteristics of MG were defined. Physiological/pharmacological studies on the transmission at the neuromuscular junction were initiated, and the concept of repetitive nerve stimulation emerged. A toxic agent was believed to be the cause of MG which appeared to resemble curare intoxication. Association of MG with thymus was noticed. No noteworthy progress was made in its treatment. In the second period (1930-1960), acetylcholine was discovered to be the transmitter at the neuromuscular junction. Repetitive nerve stimulation was used as a diagnostic test. The autoimmune nature of MG was suspected and experiments to this end started to give results. The hallmark of this period was the use of anticholinesterases and thymectomy in the treatment of MG. The third period (1960-1990) can probably be considered a revolutionary era for MG. Important immunological mechanisms (acetylcholine receptor isolation, discovery of anti-acetylcholine receptor antibodies) were clarified and the autoimmune nature of MG was demonstrated. Treatment modalities which completely changed the prognosis of MG, including positive pressure mechanic ventilation and corticosteroids as well as plasma exchange/Mg and azathioprine, were put to use. In the fourth period (1990-2020), more immunological progress, including the discovery of anti-MuSK antibodies, was achieved. Videothoracoscopic thymectomy reduced the morbidity and mortality rate associated with surgery. New drugs emerged and clinical trials were performed. Valuable guidelines were published. In the last part of the review, the experience in MG of Istanbul University, a pioneer in Turkey, is related

Sleep apnea in adult myotonic dystrophy patients who have no excessive daytime sleepiness

Sleep apnea is common in myotonic dystrophy (MD) and may cause respiratory failure. Most of the sleep studies have been performed in patients with excessive daytime sleepiness (EDS), which is a characteristic and strong predictor of sleep apnea. Therefore, we investigated the prevalence of sleep apnea in adult MD patients who have no EDS

Natural history of SMA IIIb - Muscle strength decreases in a predictable sequence and magnitude

Objective: To assess the natural progression of muscle weakness in spinal muscular atrophy (SMA) IIIb