Spinal muscular atrophies (SMAs) are a heterogeneous group of disorders characterized by muscular atrophy, weakness, and hypotonia due to suspected lower motor neuron degeneration (LMND). In a large cohort of 3,465 individuals suspected with SMA submitted for SMN1 testing to our routine diagnostic laboratory, 48.8% carried a homozygous SMN1 deletion, 2.8% a subtle mutation, and an SMN1 deletion, whereas 48.4% remained undiagnosed. Recently, several other genes implicated in SMA/LMND have been reported. Despite several efforts to establish a diagnostic algorithm for non-5q-SMA (SMA without deletion or point mutations in SMN1 [5q13.2]), data from large-scale studies are not available. We tested the clinical utility of targeted sequencing in non-5q-SMA by developing two different gene panels. We first analyzed 30 individuals with a small panel including 62 genes associated with LMND using IonTorrent-AmpliSeq target enrichment. Then, additional 65 individuals were tested with a broader panel encompassing up to 479 genes implicated in neuromuscular diseases (NMDs) with Agilent-SureSelect target enrichment. The NMD panel provided a higher diagnostic yield (33%) than the restricted LMND panel (13%). Nondiagnosed cases were further subjected to exome or genome sequencing. Our experience supports the use of gene panels covering a broad disease spectrum for diseases that are highly heterogeneous and clinically difficult to differentiate.

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Objective To evaluate if various conditions affecting the ipsilateral testis which also damage the contralateral testis share a common pathway for their effects. Materials and methods The study comprised ®ve groups of 10 adult rats which underwent surgery to produce (on their left sides); group 1, a sham operation (control); group 2, testicular torsion; group 3, vas deferens obstruction; group 4, an intra-abdominal testis; and group 5, venous obstruction. The ipsilateral and contralateral testes were harvested 4 weeks after surgery. The relative proportions of haploid cells, the mean seminiferous tubular diameter (MSTD), mean testicular biopsy scores (MTBS), and lactate and hypoxanthine levels were determined and compared. Results The proportions of haploid cells in the ipsilateral and the contralateral testes of groups 2±5 were signi®cantly lower than those of the corresponding testes of the control group. The MSTD and MTBS of the ipsilateral testes in groups 2±5 were also signi®cantly lower than the ipsilateral testes of controls and the contralateral testes within the same groups. While the MSTD and MTBS of the contralateral testes of groups 1 and 5 were not signi®cantly different, those of the contralateral testes of groups 2±4 were signi®cantly less than that of group 1. The lactic acid and hypoxanthine levels of the ipsilateral and contralateral testes were signi®cantly increased in groups 2 and 3. While only the hypoxanthine level of group 5 increased signi®cantly, both variables were not signi®cantly different between the ipsilateral testes of groups 1 and 4. Conclusions These four treatments damaged both the ipsilateral and contralateral testes. As the lactic acid and hypoxanthine levels within the contralateral testis were greater than in the controls, testicular torsion and vas deferens obstruction seem to share a common pathway (which may be a re¯ex decrease in contralateral testicular blood¯ow) for their effects on the contralateral testis.

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Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous disorders of neuromuscular transmission. Most are treatable, but certain subtypes worsen with cholinesterase inhibitors. This underlines the importance of genetic diagnosis. Here, we report on cases with genetically proven CMS from Turkey. We retrospectively reviewed our experience of all patients with CMS, referred over a 5-year period (2011–2016) to the Child Neurology Department of Dokuz Eylül University, Izmir, Turkey. In addition, PubMed was searched for published cases of genetically proven CMS originating from Turkey. In total, we identified 43 (8 new patients, 35 recently published patients) cases. Defects in the acetylcholine receptor (n=15; 35%) were the most common type, followed by synaptic basal-lamina associated (n=14; 33%) and presynaptic syndromes (n=10; 23%). We only had 3 cases (7%) who had defects in endplate development. One patient had mutation GFPT1 gene (n=1; 2%). Knowledge on CMS and related genes in Turkey will lead to prompt diagnosis and treatment of these rare neuromuscular disorders.