Background: Hyperphenylalaninemia (HPA) is an autosomal recessive disorder that results from a deficiency in the phenylalanine hydroxylase enzyme (PAH) or from a flaw in the genes that are responsible for the biosynthesis or regeneration of the cofactor tetrahydrobiopterin (BH4), including GCH1, SR, QDPR, PTS, and PCD. Identification of disease-causing variants in these genes can help physicians and clinical geneticists in differential diagnosis, appropriate prescription drugs, and saving time and cost. This study attempted to identify these genes' most prevalent disease-causing variants in Iranian HPA patients. Summary: This study was performed under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Before it started, the flow work and inclusion/exclusion criteria were published as a protocol in PROSPERO (CRD42021273705). We conducted a comprehensive search on 10/12/2022 on international online databases, including Web of Science, Scopus, EMBASE, Science Direct, PubMed/Medline, Google Scholar, SID, ISC, and Magiran search engine, to find pertinent publications. Some studies were chosen based on inclusion and exclusion criteria. Altogether, 1243 Iranian patients from 13 articles were considered. In total, we identified 129 distinct disease-causing variants in PAH (20 novel variants), 29 in QDPR (17 novel variants), 15 in PTS (seven novel variants), and one novel variant in PCD. Twenty disease-causing variants for PAH, 18 for QDPR, and eight for PTS are included in the genes' proposed genetic diagnostic panels. These panels include more than 75% of the documented disease-causing variants in the Iranian population. Key Messages: The findings of this research illustrated the spectrum of disease-causing variants in the PAH, QDPR, PTS, and PCD genes identified in Iranian HPA patients. Common disease-causing variants of these genes may be chosen as a preliminary diagnostic panel for early diagnosis and lowering therapy costs.
Background Hyperphenylalaninemia (HPA) is the most common inborn error of amino acid metabolism worldwide. At least 2% of HPA cases are caused by a deficiency in tetrahydrobiopterin (BH4) metabolism. Genes such as QDPR and PTS are essential in the BH4 metabolism. This study aims to identify disease‐causing variants in HPA patients, which may be helpful in genetic counseling and prenatal diagnosis. Methods A total of 10 HPA patients were enrolled in this study. The coding and adjacent intronic regions of PTS and QDPR genes were examined using Sanger sequencing. Protein modeling was also performed for novel identified variants. Results Ten patients and a total of 20 alleles were studied, which led to the identification of 10 different variants. All variants identified in PTS and QDPR were missense, except for the c.383_407del variant in the QDPR. Also, three novel variants were identified in the QDPR, including c.79G>T, c.383_407del and c.488G>A, and a novel variant, c.65C>G, in the PTS. Conclusions Despite the genetic similarities in the disease‐causing variants, differences were observed in the Asian and European populations with our populations; As a result, similar but more extensive studies are needed to investigate the distribution of disease‐causing variants in genes involved in non‐PKU hyperphenylalaninemia.
Spinal muscular atrophy (SMA)(OMIM#:253300) is an autosomal recessive disorder, resulting in symmetrical progressive weakness of skeletal and respiratory muscles and atrophy. The corresponding gene for the disease is the survival motor neuron 1 (SMN1) and SMN2 genes. Homozygous deletion of SMN1 exons is the most common underlying cause of the disease, and SMN2 copy numbers modify the disease phenotype. However, homozygous deletion of exon 7 of SMN1 in a completely asymptomatic individual is an extremely rare finding. The present report discusses a case of homozygote deletion of exon 7 of SMN1 in a healthy female. A healthy couple with a family history of affected family members with SMA was referred for genetic counseling. Genomic DNA was extracted from the peripheral blood of the couple and the copy number of exon 7 of the SMN1 gene was assessed for using real-time polymerase chain reaction (PCR) and PCR-Restriction fragment length polymorphism (RFLP). Assessment of SMN1-related ct in the female compared with control samples showed that the female had a homozygous deletion in the SMN1 gene. PCR-RFLP and gel electrophoresis results also confirmed the homozygous deletion of exon 7 in the female SMN1 gene. Conclusion: According to the results of this study and also other findings in previous studies, the lack of symptoms in the female with biallelic deletion of SMN1 may be related to the presence of SMN2 copies or other modifier genes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.