title: Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening.
abstract: The incidence of biotinidase deficiency in Turkey is currently one of the highest in the world. To expand upon the information about the biotinidase gene (BTD) variations in Turkish patients, we conducted a mutation screening in a large series (n = 210) of probands with biotinidase deficiency, using denaturing high-performance liquid chromatography and direct DNA sequencing. The putative effects of novel mutations were predicted by computational program. Twenty-six mutations, including six novels (p.C143F, p.T244I, c.1212-1222del11, c.1320delG, p.V457L, p.G480R) were identified. Nine of the patients were symptomatic at the initial clinical assessment with presentations of seizures, encephalopathy, and lactic acidemia. The most common mutation in this group of symptomatic patients was c.98-104 del7ins3. Among the screened patients, 72 have partial and 134 have profound biotinidase deficiency (BD) of which 106 are homozygous for BTD mutations. The common mutations (p.R157H, p.D444H, c.98-104del7ins3, p.T532M) cumulatively accounted for 72.3% of all the mutant alleles in the Turkish population.
  
  
  CONCLUSIONS
  The identification of common mutations and hot spot regions of the BTD gene in Turkish patients is important for mutation screening in the Turkish population and helps to ascertain carriers, may have impact on genetic counseling and implementing prevention programs.
authors.affiliation: Faculty of Science and Arts, Department of Biology, Aksaray University, Aksaray, Turkey, mkaraca@aksaray.edu.tr.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Karaca
authors.forename: Rıza Köksal
authors.initials: RK
authors.lastname: Özgül
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Ünal
authors.forename: Didem
authors.initials: D
authors.lastname: Yücel-Yılmaz
authors.forename: Mustafa
authors.initials: M
authors.lastname: Kılıç
authors.forename: Burcu
authors.initials: B
authors.lastname: Hişmi
authors.forename: Ayşegül
authors.initials: A
authors.lastname: Tokatlı
authors.forename: Turgay
authors.initials: T
authors.lastname: Coşkun
authors.forename: Ali
authors.initials: A
authors.lastname: Dursun
authors.forename: Hatice Serap
authors.initials: HS
authors.lastname: Sivri
mesh_terms: D000140:Acidosis, Lactic / Q000235:genetics; D043523:Biotinidase / Q000235:genetics*; D028921:Biotinidase Deficiency / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D001927:Brain Diseases / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000235:genetics; D059472:Exome; D005190:Family; D005260:Female; D006720:Homozygote; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods*; D010375:Pedigree; D012640:Seizures / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D014421:Turkey / Q000453:epidemiology
chemical_list: D004247:DNA; D043523:Biotinidase