Ultra-rare biallelic pathogenic variants in geranylgeranyl diphosphate synthase 1 (GGPS1) have recently been associated with muscular dystrophy/hearing loss/ ovarian insufficiency syndrome. Here, we describe 11 affected individuals from four unpublished families with ultra-rare missense variants in GGPS1 and provide follow-up details from a previously reported family. Our cohort replicated most of the previously described clinical features of GGPS1 deficiency; however, hearing loss was present in only 46% of the individuals. This report consolidates the disease-causing role of biallelic variants in GGPS1 and demonstrates that hearing loss and ovarian insufficiency might be a variable feature of the GGPS1-associated muscular dystrophy.
Biallelic variants of the gene encoding for the zinc-finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying
Background: Diabetes mellitus (DM) is a growing epidemic metabolic syndrome, which affects near 5.6% of the world's population. Almost 12% of health expenditure is dedicated to this disorder. Discovering and developing biomarkers as a practical guideline with high specificity and sensitivity for the diagnosis, prognosis, and clinical management of DM is one of the subjects of great interest among DM researchers due to the long-lasting asymptomatic clinical manifestation of DM. In this study, we described a recently identified molecular biomarker involved in DM.Methods: This review study was done at the Diabetes Research Center affiliated to Shahid Sadoughi University of Medical Sciences. PubMed, Scopus, Google Scholar, and Web of Science were searched using the following keywords: "diabetes mellitus", "biomarker", "microRNA", "diagnostic tool" and "clinical manifestation."Results: A total of 107 studies were finally included in this review. After evaluating numerous articles, including original, metaanalysis, and review studies, we focused on molecular biomarkers involved in DM diagnosis and management.
Conclusion:Increasing interest in biomarkers associated with DM goes back to its role in decreasing diabetes-related morbidity and mortality. This review focused on major molecular biomarkers such as proteomic and microRNA (miRNAs) as novel and interesting DM biomarkers that can help achieve timely diagnosis of DM.
Background: Intellectual disability (ID) is a heterogeneous group of neurodevelopmental disorders that is characterized by significant impairment in intellectual and adaptive functioning with onset during the developmental period. Whole-exome sequencing (WES)-based studies in the consanguineous families with individuals affected with ID have shown a high burden of relevant variants. So far, over 700 genes have been reported in syndromic and non-syndromic ID. However, genetic causes in more than 50% of ID patients still remain unclear.Methods: Whole-exome sequencing was applied for investigation of various variants of ID, then Sanger sequencing and in silico analysis in ten patients from five Iranian consanguineous families diagnosed with autosomal recessive neurodevelopmental disorders, intellectual disability, performed for confirming the causative mutation within the probands. The most patients presented moderate-to-severe intellectual disability, developmental delay, seizure, speech problem, high level of lactate, and onset before 10 years.
Results:Filtering the data identified by WES, two novel homozygous missense variants in FBXO31 and TIMM50 genes and one previously reported mutation in the CEP290 gene in the probands were found. Sanger sequencing confirmed the homozygote variant's presence of TIMM50 and FBXO31 genes in six patients and two affected siblings in their respective families. Our computational results predicted that the variants are located in the conserved regions across different species and have the impacts on the protein stability.
Conclusion:Hence, we provide evidence for the pathogenicity of two novel variants in the patients which will expand our knowledge about potential mutation involved in the heterogeneous disease.
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