Allelic dropout in PAH affecting the results of genetic diagnosis in phenylketonuria
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Lin Wang
Abstract
Objectives
Phenylketonuria (PKU) is an inherited autosomal recessive disorder of phenylalanine metabolism. It is mainly caused by a deficiency in phenylalanine hydroxylase (PAH) and frequently diagnosed with Sanger sequencing. To some extent, allelic dropout can explain the inconsistency in genotype and phenotype.
Methods
Three families were evaluated through DNA sequence analysis, multiplex ligation-dependent probe amplification (MLPA) and prenatal diagnosis technologies. The possibility of inconsistency in phenotype and genotype with c.331C>T variant was analysed.
Results
Through pedigree analysis, three mothers carried a homozygous c.331C>T variant, which was a false-positive result. New primers were used, and this error was caused by allelic dropout. In this case, c.158G>A was likely a benign variant.
Conclusions
Sequence variants in primer-binding regions could cause allelic dropout, creating unpredictable errors in genotyping. Our results emphasised the need for careful measures to treat genotype–phenotype inconsistencies.
Funding source: Shaanxi Provincial Science and Technology Department
Award Identifier / Grant number: 2017SF-206
Award Identifier / Grant number: 2021SF195
Acknowledgments
The authors thank all the patients and their families. We express our gratitude to all of the pediatricians who helped with the study.
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Research funding: This work was supported by the “Shaanxi Provincial Science and Technology Department (2017SF-206 and 2021SF195).
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: All authors declare that they have no conflicts of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: Approval was granted by the Ethics Committee of the Northwest Women’s and Children’s Hospital, and documented in case NO. 20-022. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2021-0336).
© 2022 Walter de Gruyter GmbH, Berlin/Boston
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Articles in the same Issue
- Frontmatter
- Review Article
- Congenital hyperinsulinism: recent updates on molecular mechanisms, diagnosis and management
- Original Articles
- Weight changes of children in 1 year during COVID-19 pandemic
- Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease
- Rates of adrenal insufficiency using a monoclonal vs. polyclonal cortisol assay
- Hyperinsulinemic hypoglycemia in growth restricted convalescent preterm neonates: clinical characteristics and impediments to early diagnosis
- Identification of three novel pathogenic mutations in cystathionine beta-synthase gene of Pakistani intellectually disabled patients
- The prevalence of incidental finding of gynecomastia on thoracic computed tomography in the pediatric age group
- The prevalence of hypertension and elevated blood pressure and its correlation with overweight/obesity among students aged 6–17 years in Suzhou
- Investigation of androgen receptor gene CAG repeat length polymorphism in pubertal gynecomastia
- A single-centre study of genetic mutations, audiology, echocardiogram and pulmonary function in Saudi children with osteogenesis imperfecta
- A 10-year retrospective single-center study of alpha-fetoprotein and beta-human chorionic gonadotropin in Romanian children with (para)gonadal tumors and cysts
- Clinical, pathological and molecular spectrum of patients with glycogen storage diseases in Pakistan
- Allelic dropout in PAH affecting the results of genetic diagnosis in phenylketonuria
- Short Communication
- Role of the SARS-CoV-2 virus in the appearance of new onset type 1 diabetes mellitus in children in Gran Canaria, Spain
- Case Reports
- 3-M syndrome – a primordial short stature disorder with novel CUL7 mutation in two Indian patients
- The coincidence of two rare diseases with opposite metabolic phenotype: a child with congenital hyperinsulinism and Bloom syndrome
- Growth hormone deficiency in a child with benign hereditary chorea caused by a de novo mutation of the TITF1/NKX2-1 gene
- Identification of a novel mutation in the PHKA2 gene in a child with liver cirrhosis
