Effect of growth hormone on muscle strength, tone and mobility of children with Prader-Willi syndrome

ObjectivePrader-Willi Syndrome (PWS) is a genetic syndrome presenting with severe hypotonia and decreased agility. Growth Hormone (GH), which is often used in these patients to treat short stature and obesity, seems improve hypotonia, physical strength, activity, and locomotor developmental ability. The aim ofthis study was to find the effects of growth hormone on agility and strength of these patients.Material & MethodsIn a prospective randomized controlled clinical trial in an out-patient pediatric endocrine clinic in Tehran, 21 PWS children (12 boys and 9 girls, 4 to 9 years old) were divided into either GH-treated or control groups and followed for two years. Agility run, sit ups, weight lifting, and inspiratory and expiratory strength were considered as the main outcome measures.ResultsAll the outcome measures of the GH treated group showed a significant improvement compared to the control group.ConclusionGH causes a significant improvement in agility and strength of PWS children.Key words: Preder-willi syndrome; PWS; growth hormone;agility; strengt

Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review

Abstract Background Pontocerebellar hypoplasia is an umbrella term describing a heterogeneous group of prenatal neurodegenerative disorders mostly affecting the pons and cerebellum, with 17 types associated with 25 genes. However, some types of PCH lack sufficient information, which highlights the importance of investigating and introducing more cases to further elucidate the clinical, radiological, and biochemical features of these disorders. The aim of this study is to provide an in-depth review of PCH and to identify disease genes and their inheritance patterns in 12 distinct Iranian families with clinically confirmed PCH. Methods Cases included in this study were selected based on their phenotypic and genetic information available at the Center for Comprehensive Genetic Services. Whole-exome sequencing (WES) was used to discover the underlying genetic etiology of participants' problems, and Sanger sequencing was utilized to confirm any suspected alterations. We also conducted a comprehensive molecular literature review to outline the genetic features of the various subtypes of PCH. Results This study classified and described the underlying etiology of PCH into three categories based on the genes involved. Twelve patients also were included, eleven of whom were from consanguineous parents. Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features. Strabismus and elevation in lactate levels in MR spectroscopy were novel phenotypes for the first time in PCH types 7 and 9. Conclusions This study merges previously documented phenotypes and genotypes with unique novel ones. Due to the diversity in PCH, we provided guidance for detecting and diagnosing these heterogeneous groups of disorders. Moreover, since certain critical conditions, such as spinal muscular atrophy, can be a differential diagnosis, providing cases with novel variations and clinical findings could further expand the genetic and clinical spectrum of these diseases and help in better diagnosis. Therefore, six novel genetic variants and novel clinical and paraclinical findings have been reported for the first time. Further studies are needed to elucidate the underlying mechanisms and potential therapeutic targets for PCH

The genetic basis of early-onset hereditary ataxia in Iran: results of a national registry of a heterogeneous population

Abstract Background To investigate the genetics of early-onset progressive cerebellar ataxia in Iran, we conducted a study at the Children’s Medical Center (CMC), the primary referral center for pediatric disorders in the country, over a three-year period from 2019 to 2022. In this report, we provide the initial findings from the national registry. Methods We selected all early-onset patients with an autosomal recessive mode of inheritance to assess their phenotype, paraclinical tests, and genotypes. The clinical data encompassed clinical features, the Scale for the Assessment and Rating of Ataxia (SARA) scores, Magnetic Resonance Imaging (MRI) results, Electrodiagnostic exams (EDX), and biomarker features. Our genetic investigations included single-gene testing, Whole Exome Sequencing (WES), and Whole Genome Sequencing (WGS). Results Our study enrolled 162 patients from various geographic regions of our country. Among our subpopulations, we identified known and novel pathogenic variants in 42 genes in 97 families. The overall genetic diagnostic rate was 59.9%. Notably, we observed PLA2G6, ATM, SACS, and SCA variants in 19, 14, 12, and 10 families, respectively. Remarkably, more than 59% of the cases were attributed to pathogenic variants in these genes. Conclusions Iran, being at the crossroad of the Middle East, exhibits a highly diverse genetic etiology for autosomal recessive hereditary ataxia. In light of this heterogeneity, the development of preventive strategies and targeted molecular therapeutics becomes crucial. A national guideline for the diagnosis and management of patients with these conditions could significantly aid in advancing healthcare approaches and improving patient outcomes

Additional file 1 of Broadening the phenotype and genotype spectrum of novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review

Additional file 1: Supplementary Figure 1. Flowchart of included cases in this study. Supplementary Figure 2. Variant filtering and pathogenicity evaluation algorithm. Supplementary Figure 3. Pedigree of included cases in this study. Pedigree a-k are cases 1-12, respectively. The proband is shown by an arrow in each pedigree. Circle and squares represent female and male, respectively. People with same color in each pedigree have same clinical manifestations. Supplementary Figure 4. The structure of protein [1] included in this study and the position of mutated amino acid. a) Structure of human nuclear RNA exosome (PDB: 6H25) [2]. EXOS3 is shown by an arrow and the position of Asp132 which is substituted with Ala in case 1 and 2 b) Structure human tRNA Splicing Endonuclease (TSEN) Complex (PDB: 7UXA) [3]. TSEN2 and TSEN54 are shown by arrows c) Structure of human holo SepSecS (PDB: 7L1T) [4] and the position of Cys70 and His425 which are substituted with Arg in case 4 and 5 d) Structure of AMP deaminase 2 (PDB: 8HUB)[5] and the position of Arg 620 which is substituted with Ser in case 8 e) Structure of CLP1(Swiss model: Q92989) [6] and the position of Leu262 which is substituted with Val in case 9 and Arg140 which is substituted with His in case 10 and 11 f) Structure of TBC1D23 N terminal domain (PDB: 6JL7) [7] and the position of Met 153 which is substituted with Thr in case 12