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Molecular genetics of a cohort of 635 cases of phenylketonuria in a consanguineous population
Author(s) -
Shirzadeh Tina,
Saeidian Amir Hossein,
Bagherian Hamideh,
Salehpour Shadab,
Setoodeh Aria,
Alaei Mohammad Reza,
Youssefian Leila,
Samavat Ashraf,
Touati Andrew,
Fallah MohammadSadegh,
Vahidnezhad Hassan,
Karimipoor Morteza,
Azadmehr Sarah,
Raeisi Marzieh,
Bandehi Sarhadi Ameneh,
Zafarghandi Motlagh Fatemeh,
Jamali Mojdeh,
Zeinali Zahra,
Abiri Maryam,
Zeinali Sirous
Publication year - 2018
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-018-0228-6
Subject(s) - phenylalanine hydroxylase , hyperphenylalaninemia , inborn error of metabolism , genetics , human genetics , uniparental disomy , genetic counseling , newborn screening , molecular genetics , medical genetics , medicine , prenatal diagnosis , population , mendelian inheritance , consanguinity , genetic heterogeneity , genetic testing , gene , biology , pregnancy , endocrinology , phenylalanine , chromosome , phenotype , fetus , karyotype , environmental health , amino acid
Phenylketonuria (PKU) is an inborn error of amino acid metabolism caused by mutations in the phenylalanine hydroxylase ( PAH ) gene, characterized by intellectual deficit and neuropsychiatric complications in untreated patients with estimated frequency of about one in 10,000 to 15,000 live births. PAH deficiency can be detected by neonatal screening in nearly all cases with hyperphenylalaninemia on a heel prick blood spot. Molecular testing of the PAH gene can then be performed in affected family members. Herein, we report molecular study of 635 patients genetically diagnosed with PKU from all ethnicities in Iran. The disease‐causing mutations were found in 611 (96.22%) of cases. To the best of our knowledge, this is the most comprehensive molecular genetics study of PKU in Iran, identifying 100 distinct mutations in the PAH gene, including 15 previously unreported mutations. Interestingly, we found unique cases of PKU with uniparental disomy, germline mosaicism, and coinheritance with another Mendelian single‐gene disorder that provides new insights for improving the genetic counseling, prenatal diagnosis (PND), and/or pre‐implantation genetic diagnosis (PGD) for the inborn error of metabolism group of disorders.