Dataset Information

A Novel Variant in the PAH Gene Causing Phenylketonuria in an Iranian Pedigree.

ABSTRACT: BACKGROUND:Phenylalanine hydroxylase (PAH) gene is the well-known causative gene for classic Phenylketonuria (PKU) (OMIM#261600) disease, with more than 500 reported mutations. Through this study, a novel mutation in the PAH gene in an Iranian pedigree with phenylketonuria was introduced. METHODS:A consanguineous family with a 10-year old affected girl was referred for genetic analysis. Mutation screening of all exons and exon-intron boundaries was performed by Sanger sequencing, and mini haplotype analysis was carried out by genotyping of Short Tandem Repeat (STR) and Variable Number Tandem Repeat (VNTR) alleles. RESULTS:Mutation analysis revealed a novel homozygous insertion of a single adenine nucleotide at position 335 in exon 3 of the PAH gene. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the change is interpreted as a pathogenic mutation which produces a premature termination signal (TAA) at codon 113 according to in silico assessments. The mini haplotype analysis showed that this mutation was linked to STR (15) -VNTR (3). CONCLUSION:In this study, a novel mutation was reported in a patient who had PKU symptoms without any previously reported mutations in the PAH gene (NM_000277.1:p.Asp112Glufs*2) that can be responsible for the classical PKU phenotype in the Iranian population. Detection of novel mutations indicates notable allelic heterogeneity of the PAH locus among this population.

SUBMITTER: Alavinejad E

PROVIDER: S-EPMC5501143 | biostudies-literature | 2017 Jul-Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Novel Variant in the <i>PAH</i> Gene Causing Phenylketonuria in an Iranian Pedigree.

Alavinejad Elaheh E Sajedi Seyede Zahra SZ Razipour Masoumeh M Entezam Mona M Mohajer Neda N Setoodeh Aria A Talebi Saeed S Keramatipour Mohammad M

Avicenna journal of medical biotechnology 20170701 3

<h4>Background</h4><i>Phenylalanine hydroxylase (PAH)</i> gene is the well-known causative gene for classic Phenylketonuria (PKU) (OMIM#261600) disease, with more than 500 reported mutations. Through this study, a novel mutation in the <i>PAH</i> gene in an Iranian pedigree with phenylketonuria was introduced.<h4>Methods</h4>A consanguineous family with a 10-year old affected girl was referred for genetic analysis. Mutation screening of all exons and exon-intron boundaries was performed by Sange ...[more]

PMID: 28706611

Similar Datasets

Project description:BACKGROUND:Phenylketonuria (PKU) is an autosomal recessive disease resulting from mutations in the PAH gene. Most of the patients are compound heterozygotes, and genotype is a major factor in determining the phenotypic variability of PKU. More than 1,000 variants have been described in the PAH gene. Rio de Janeiro's population has a predominance of Iberian, followed by African and Amerindian ancestries. It is expected that most PKU variants in this Brazilian state have originated in the Iberian Peninsula. However, rare European, African or pathogenic variants that are characteristic of the admixed population of the state might also be found. METHODS:A total of 102 patients were included in this study. Genomic DNA was isolated from dried blood spots. Sanger sequencing was used for PAH gene variant identification. Deletions and duplications were also screened using MLPA analysis. Haplotypes were also determined. RESULTS:Nine (8.8%) homozygous and 93 (91.2%) compound heterozygous patients were found. The spectrum included 37 causative mutations. Missense, nonsense, and splicing pathogenic variants corresponded to 63.7%, 2.9%, and 22.6% of the mutant alleles, respectively. Large (1.5%), and small deletions, inframe (5.4%) and with frameshift (3.9%), comprised the remainder. The most frequent pathogenic variants were: p.V388M (12.7%), p.R261Q (11.8%), IVS10-11G>A (10.3%), IVS2+5G>C (6.4%), p.S349P (6.4%), p.R252W (5.4%), p.I65T (4.4%), p.T323del (4.4%), and p.P281L (3.4%). One novel variant was detected: c.934G>T (p.G312C) [rs763115697]. CONCLUSION:The three most frequent pathogenic variants in our study (34.8% of the alleles) were also the most common in other Brazilian states, Portugal, and Spain (p.V388M, p.R261Q, IVS10-11G>A), corroborating that the Iberian Peninsula is the major source of PAH mutations in Rio de Janeiro. Pathogenic variants that have other geographical origins, such IVS2+5G>C, p.G352Vfs*48, and IVS12+1G>A were also detected. Genetic drift and founder effect may have also played a role in the mutation spectrum we observed.

Dataset Information

A Novel Variant in the PAH Gene Causing Phenylketonuria in an Iranian Pedigree.

Publications

A Novel Variant in the <i>PAH</i> Gene Causing Phenylketonuria in an Iranian Pedigree.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure