Exome sequencing revealed variants in SGCA and SIL1 genes underlying limb girdle muscular dystrophy and Marinesco-Sjögren syndrome patients.

BACKGROUND: Inherited neuromuscular (NMD) and neurodegenerative diseases (NDD) belong to two distinct categories that disturb different components of the nervous system, leading to a variety of different symptoms and clinical manifestations. Both NMD and NDD are a heterogeneous group of genetic conditions. Genetic variations in the SGCA and SIL1 genes have been implicated in causing Limb Girdle Muscular Dystrophy (LGMD), a type of neuromuscular disorder, and Marinesco-Sjögren Syndrome (MSS) which is a neurodegenerative disorder. METHODS: In the present study, we have investigated four patients presenting LGMD and five patients with MSS features. After collecting detailed clinical and family history, necessary laboratory investigations, including estimation of a skeletal muscle marker enzyme serum creatine kinase (CK), nerve conduction study (NCS), electromyography (EMG), echocardiography (Echo), Magnetic resonance imaging (MRI -brain), CT-brain and X-rays were performed. Whole exome followed by Sanger sequencing was employed to search for the disease-causing variants. RESULTS: Physical examination in LGMD patients revealed poor muscle tone and facing difficulty in straightening up from the floor. Clinical history revealed frequent falls and strenuousness in climbing stairs. They started toe-walking in early childhood. Laboratory investigations confirmed elevated CK levels and abnormal NCS and EMG. The MSS patients showed abnormalities in gate and jerking movement, abnormal speech, and strabismus with cataract. MRI-brain showed cerebral atrophy in some MSS patients with elevated CK levels. Whole exome sequencing revealed a nonsense variant [c.C574T, p.(Arg192*)] in the SGCA gene and a frameshift [c.936dupG, p.(Leu313AlaFs*39)] in the SIL1 gene in LGMD and MSS patients, respectively. CONCLUSION: Our study emphasizes the significance of integrating clinical and genetic analyses for precise diagnosis and tailored management strategies in inherited NMD and NDD disorders. To the best of our knowledge, this is the first study documenting SGCA and SIL1 recurrent variants in subcontinent populations with few rare clinical features. The recurrent mutations expanding the global understanding of the mutation's geographic and ethnic distribution and contributing valuable epidemiological data. The study will facilitate genetic counseling for families experiencing similar clinical features, both within Pakistani populations and in other regions.

A Convenient Synthesis of Short α-/ß-Mixed Peptides as Potential α-Amylase Inhibitors.

Over the last decades, the increased incidence of metabolic disorders, such as type two diabetes and obesity, has motivated researchers to investigate new enzyme inhibitors. Inhibition of the α-amylase enzyme is one therapeutic approach in lowering glucose levels in the blood to manage diabetes mellitus. The objective of this study was to synthesize short α-/ß-mixed peptides in the solution phase. The Boc-protected α-L-leucine was converted to ß-analogue by using Arndt-Eistert synthesis with the advantage of no racemization and retention of configuration. Three novel short peptides were successfully synthesized: N(Boc)-Gly-ß-Leu-OCH3(14), N(Boc)-O(Bz)α-Ser-ß-Leu-OCH3(16), and N(Boc)-O(Bz)-α-Tyr-α-Gly-ß-Leu-OCH3(17), characterized by FTIR and 1H NMR analysis. The synthesized peptide 16 showed highest inhibitory activity (45.22%) followed by peptide 14 (18.51%) and peptide 17 (17.05%), respectively. Intriguingly, peptide 16 showed higher inhibition on α-amylase compared with other α-/ß-mixed peptides.

Harvesting Costal Cartilage for Secondary Rhinoplasty: Techniques, Considerations, and Outcomes.

Secondary rhinoplasty is a surgical procedure aimed at reshaping the nose after the unsatisfactory results of primary rhinoplasty, which usually requires a reliable source of cartilage for grafting. Septal cartilage is usually the first option for rhinoplasty, but in cases where it is insufficient, rib cartilage might be used, which is the focus of the current study. The article details the surgical techniques for rib cartilage harvesting, highlighting the preference for the seventh rib done under general anaesthesia. The surgery requires a precise incision, harvesting of the cartilage, and careful closure while the cartilage is stored in a saline solution until use. It also introduces innovative approaches to minimize complications and improve patient satisfaction, including trans-umbilical endoscopic harvesting, the use of the 10th rib to reduce morbidity, and employing fresh frozen homologous rib cartilage as a grafting alternative. Based on various studies, most cases following rhinoplasty with rib cartilage showed a high satisfaction rate despite the complexity of the procedure. Patient consideration includes good communication with realistic expectations through imaging techniques. We also discuss complications, which can heavily impact the patient's quality of life. We hope that by providing this information, our paper will provide surgeons and researchers with the latest information on this topic.