Prenatal Diagnosis of Tyrosinemia Type 1 Using Next Generation Sequencing.
Prenatal diagnosis using conventional molecular genetic techniques may be encountered with some limitations when the disease causing mutation is unknown. Here, we report on prenatal diagnosis of tyrosinemia in a family with consanguineous marriage and two affected children in whom no disease causing mutation had been identified before pregnancy. Mutation analyses of three genes associated with tyrosinemia including FAH, TAT and HPD were carried out in the fetal DNA sample using Next Generation Sequencing. A heterozygous nonsense mutation (p.Arg237Ter) in FAH gene was detected in the fetus. Further investigations suggested that the fetus was carrier of tyrosinemia type 1. This study demonstrates the successful application of Next Generation Sequencing in prenatal diagnosis, when the time is a limiting factor, more than one (especially large) responsible genes are involved, a "founder" or a "previously detected" mutation is not present and hence the conventional molecular genetic investigations cannot be employed.
a Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR , Tehran , Iran.|b Comprehensive Genetic Center, Hope Generation Foundation , Tehran , Iran.|c Gene Clinic , Tehran , Iran.
Maryam
M
Rafati
a Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR , Tehran , Iran.|d Department of Medical Genetics , Tehran University of Medical Sciences , Tehran , Iran.
Faezeh
F
Mohamadhashem
a Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR , Tehran , Iran.|b Comprehensive Genetic Center, Hope Generation Foundation , Tehran , Iran.
Azadeh
A
Hoseini
b Comprehensive Genetic Center, Hope Generation Foundation , Tehran , Iran.
Somayeh Darzi
SD
Ramandi
a Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR , Tehran , Iran.|b Comprehensive Genetic Center, Hope Generation Foundation , Tehran , Iran.|c Gene Clinic , Tehran , Iran.
Saeed Reza
SR
Ghaffari
D018389:Codon, Nonsense; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree; D011296:Prenatal Diagnosis; D020176:Tyrosinemias / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
D018389:Codon, Nonsense; D006867:Hydrolases; C020156:fumarylacetoacetase
FAH gene; Next Generation Sequencing; prenatal diagnosis; tyrosinemia