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Glutaric acidemia type I (GA-1) is an inborn error of metabolism due to deficiency of glutaryl-CoA dehydrogenase (GCDH), which catalyzes the conversion of glutaryl-CoA to crotonyl-CoA. GA-1 occurs in about 1 in 100 000 infants worldwide. The GCDH gene is on human chromosome 19p13.2, spans about 7 kb and comprises 11 exons and 10 introns. Tandem mass spectrometry (MS/MS) was used for clinical diagnosis in a proband from Iran with GA-1. Sanger sequencing was performed using primers specific for coding exons and exon-intron flanking regions of the GCDH gene in the proband. Cosegregation analysis and in silico assessment were performed to confirm the pathogenicity of the candidate variant. A novel homozygous missense variant c.1147C > A (p.Arg383Ser) in exon 11 of GCDH was identified. Examination of variant through in silico software tools determines its deleterious effect on protein in terms of function and stability. The variant cosegregates with the disease in family. In this study, the clinical and molecular aspects of GA-1 were investigated, which showed one novel mutation in the GCDH gene in an Iranian patient. The variant is categorized as pathogenic according to the the guideline of the American College of Medical Genetics and Genomics (ACMG) for variant interpretation. This mutation c.1147C > A (p.Arg383Ser) may also be prevalent among Iranian populations.

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It is found that the death of retinal photoreceptors is the main cause of retinal degeneration, while there is not an effective treatment protocol. Data of preclinical and clinical trials indicates that the stem cell therapy is a useful way of treating retinal degeneration problems. On the other hand, previous works found that miRNA-182, -183 significantly affected the photoreceptor maturation and maintenance in animal models. The present study aimed to investigate the impact of a temporary increase in miRNA-182, -183 expression on the differentiation of human bone marrow mesenchymal stem cells (hBMSCs) into photoreceptor-like cells. To this end, miRNA-182, -183 was transfected into hBMSCs; then, qRT-PCR was performed to measure the expression levels of miRNA-182, -183 and some retina-specific genes such as OTX2, NRL, PKCα, and recoverin. CRX and rhodopsin (RHO) levels were also measured through qRT-PCR and immunocytochemistry We indicated that the transfection of hBMSCs with miRNA-182, -183 using the Lipofectamine induce differentiation and progenitor’s genes expression consisted of CRX, OTX2, PKC, Recoverin, NRL and RHO. Moreover, the upregulation expression of transcription factors, CRX and RHO, indicated that miRNA-182, -183 could serve as crucial functions in the differentiation of hBMSCs into photoreceptor-like cells. The findings may provide a new strategy to improve the usage of hBMSCs as a treatment for the retinal dysfunction.