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Background: Hyperphenylalaninemia (HPA) is a metabolic disorder classified into phenylalanine‐4‐hydroxylase (PAH) and non‐PAH deficiency. The latter is produced by mutations in genes involved in the tetrahydrobiopterin (BH4) biosynthesis pathway and DNAJC12 pathogenetic variants. The BH4 metabolism, including de novo biosynthesis involved genes (i.e., guanosine 5′‐triphosphate cyclohydrolase I (GTPCH/GCH1), sepiapterin reductase (SR/SPR), 6‐pyruvoyl‐tetrahydropterin synthase (PTPS/PTS)), and two genes that play roles in cofactor regeneration pathway (i.e., dihydropteridine reductase (DHPR/QDPR) and pterin‐4α‐carbinolamine dehydratase (PCD/PCBD1)). The subsequent systemic hyperphenylalaninemia and monoamine neurotransmitter deficiency lead to neurological consequences. The high rate of consanguineous marriages in Iran substantially increases the incidence of BH4 deficiency. Methods: We utilized the Sanger sequencing technique in this study to investigate 14 Iranian patients with non‐PAH deficiency. All affected subjects in this study had HPA and no mutation was detected in their PAH gene. Results: We successfully identified six mutant alleles in BH4‐deficiency‐associated genes, including three novel mutations: one in QDPR, one in PTS, and one in the PCBD1 gene, thus giving a definite diagnosis to these patients. Conclusion: In this light, appropriate patient management may follow. The clinical effect of reported variants is essential for genetic counseling and prenatal diagnosis in the patients' families and significant for the improvement of precision medicine. [ABSTRACT FROM AUTHOR]

Background. As an autosomal recessive disease, phenylketonuria (PKU) is caused by deficiency in phenylalanine hydroxylase (PAH) gene. The incidence of different mutations in phenylalanine hydroxylase is associated with differences in race and ethnicity. The aim of this study is to investigate the mutation spectrum in hotspot region of PAH gene in PKU patients. Materials and Method. For this purpose, we studied exons 6, 7, 10–11 and 12 and adjacent flanking regions of PAH gene from a total of 26 unrelated hyperphenylalaninemia patients (13 males and 13 females) in Golestan province using PCR-sequencing method. Results. Among 26 analyzed patients, 11 distinct mutations were found in combinations of 18 genotypes. A mutation detection rate of 64% was achieved. The high heterogeneity of PKU was reported in this study. The most prevalent mutations were IVS10-11G>A (19.23%), followed by IVS11+1G>C, p.P416HfsX36 and p.R261Q which accounted for 66.67% of mutant alleles. IVS9-1G>T and p.P416HfsX36 are novel mutations. Exonic polymorphisms L385L and Q232Q and intronic polymorphisms IVS10+155T>C, IVS10+156T>G, and IVS10-193G>C were found to have high frequency. Conclusion. A mutation spectrum with high frequency was predicted in Northern region of Iran due to its ethnic heterogeneity. Furthermore, it seems that the presence of some mutations in Golestan province indicates gene flow between Iran and the neighboring countries. [ABSTRACT FROM AUTHOR]

Simple Summary: The BMPR1B gene is one of the major genes involved in controlling prolificacy in small ruminant species. The research was conducted to detect possible polymorphisms in BMPR1B gene in a population of Markhoz goats, a valuable genetic resource of Iran. The results showed that all the analyzed individuals did not carry the previously reported FecB mutant allele. Moreover, we reported for the first time two novel possible mutations in exon 8 of BMPR1B gene that are noteworthy of further investigation. Reproductive traits in livestock species are genetically controlled by the action of single genes with a major effect, commonly known as fecundity genes. One of the genes involved in controlling prolificacy is BMPR1B (FecB), a dominant autosomal gene located in chromosome 6 responsible for the fecundity and twinning rate in sheep and goat species. Markhoz goat is a valuable Iranian genetic resource endangered by extinction. Increasing the genetic variability and reproductive performances of Markhoz goat could preserve and enhance its economic value. This study was carried out to detect possible polymorphisms in BMPR1B gene in a sample of 100 Markhoz goats from Iran. DNA samples were screened by PCR–RFLP to assess the presence of the previously reported FecB mutation. Finally, the amplicons from seven goats out of the 100 samples were sequenced. The results showed that all the analyzed individuals did not carry the previously reported FecB mutant allele. However, our findings revealed two novel possible mutations in exon 8 of BMPR1B gene (775A > G and 777G > A) that need further investigations. [ABSTRACT FROM AUTHOR]