Dataset Information

Genetic evaluation of hyperphenylalaninemia patients with tetrahydrobiopterin deficiency in Iranian population: Identification of four novel disease-causing variants.

ABSTRACT:

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.

SUBMITTER: Sadat Fatemi SH

PROVIDER: S-EPMC9747554 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Genetic evaluation of hyperphenylalaninemia patients with tetrahydrobiopterin deficiency in Iranian population: Identification of four novel disease-causing variants.

Sadat Fatemi Seyedeh Helia SH Eshraghi Peyman P Ghanei Mahmoud M Hamzehloei Tayebeh T

Molecular genetics & genomic medicine 20221116 12

<h4>Background</h4>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.<h4>Methods</h4>A total of 10 HPA patients were enrolled in this study. The coding and adjac ...[more]

PMID: 36382472

Similar Datasets

Project description:Background and purposeSevere and progressive neurologic disease remains a problem for patients with hyperphenylalaninemia due to a deficiency of tetrahydrobiopterin (BH4), even with early diagnosis and despite treatment with BH4 and neurotransmitter precursors. Few reports have included the associated imaging characteristics. Our purpose was to describe the imaging features of BH4-deficient patients identified by neonatal screening in a Taiwanese population and to correlate the imaging features with the treatment.MethodsThis study analyzed the cases of eight BH4-deficient patients who were examined by MR imaging and MR spectroscopy. Analysis of the findings was correlated with the clinical findings.ResultsOne patient whose intelligence quotient score was lower than those of the other seven patients experienced seizures in conjunction with central white matter signal changes on MR images and a lactate peak on MR spectroscopy. Lactate peak was revealed in another patient who had marked elevations of N-acetylaspartate:creatine and N-acetylaspartate:choline ratios. Although most patients had a higher than average N-acetylaspartate:creatine or N-acetylaspartate:choline ratio, the patient who had decreases of both ratios possessed the highest intelligence quotient scores among the eight patients. In addition, the myoinositol:choline ratio correlated positively with the average BH4 dosage (P =.027, r = 0.027) and the choline:creatine ratio correlated negatively with the average 5-hydroxytryptophan dosage (P =.035, r = -0.742).ConclusionCompared with classical phenylketonuria, patients with BH4 deficiency have fewer white matter changes revealed by MR imaging but more changes revealed by MR spectroscopy. MR spectroscopy is a potential method with which to monitor the dosages of supplements used to treat this disorder. In addition, MR spectroscopy may be helpful in gaining understanding of the neurophysiological changes that occur in association with this disease.

Dataset Information

Genetic evaluation of hyperphenylalaninemia patients with tetrahydrobiopterin deficiency in Iranian population: Identification of four novel disease-causing variants.

Background

Methods

Results

Conclusions

Publications

Genetic evaluation of hyperphenylalaninemia patients with tetrahydrobiopterin deficiency in Iranian population: Identification of four novel disease-causing variants.

Similar Datasets

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