Molecular Diagnostics of Hereditary Unconjugated Hyperbilirubinemias in Slovakia
Authors:
I. Zmetáková; I. Čierna; D. Székyová; G. Minárik; A. Ficek; H. Poláková; V. Ferák; E. Feráková; Ľ. Kádaši; L. Kovács
Authors place of work:
2. detská klinika Lekárskej fakulty Univerzity Komenského a Detskej fakultnej nemocnice, Bratislava
prednosta prof. MUDr. L. Kovács, DrSc., MPH
; Katedra molekulovej biológie Prírodovedeckej fakulty UK v Bratislave a Ústav molekulárnej fyziológie a genetiky SAV, Bratislava
vedúci doc. RNDr. Ľ. Kádaši, DrSc.
Published in the journal:
Čes-slov Pediat 2009; 64 (5): 223-229.
Category:
Original Papers
Summary
Known forms of hereditary unconjugated hyperbilirubinemias are symptomatically and prognostically diverse defects of bilirubin metabolism caused by various alterations of the UGT1 gene, which codes for the enzyme uridine diphosphoglucuronosyl transferase. The aim of the present work was to determine the spectrum of molecular alterations that contribute to their development in Slovak population.
Patients and methods:
Presence of insertion A(TA)7TAA and substitution T-3279G in the regulating areas of the UGT1A1 gene was determined in DNA samples from 110 unrelated subjects with clinically diagnosed Gilbert’s syndrome and from 240 clinically asymptomatic Slovak control subjects of both Gypsy and Non-Gypsy origin (120 and 120 subjects). In addition to this, mutation analysis of the UGT1A1 gene was accomplished in two unrelated Slovak kindreds with clinically diagnosed Crigler-Najjar syndrome type I.
Results:
101 of 110 (91.8%) patients with Gilbert’s syndrome were homozygotes for both the insertional A(TA)7TAA as well as the substitutional T-3279G polymorphism detected in the UGT1A1 gene (allelic frequency 0.95). The allelic frequency of the A(TA)7TAA polymorphism was identical (q = 0.36 and p = 0.64) in control subjects of both Gypsy and Non-Gypsy origin that corresponds in this population to an expected frequency of homozygotes for A(TA)7TAA insertion of 12.9 %. In one of the two unrelated Slovak kindreds with Crigler-Najjar syndrome type I we found a homozygous deletion 1220delA in exon 4 of the UGT1A1 gene (kindred A). Affected subjects from kindred B carried two different deletions (717-718delAG in exon 1 and 1220delA in exon 4) in gene UGT1A1.
Conclusion:
Available molecular analysis of the UGT1A1 gene has an important role for exact clinical diagnosis of Gilbert’s syndrome and contributed to prenatal diagnosis of Criegler-Najjar syndrome in affected kindreds.
Key words:
hereditary unconjugated hyperbilirubinemias, Gilbert’s syndrome, Criegler-Najjar syndrome, genetics
Zdroje
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Štítky
Neonatology Paediatrics General practitioner for children and adolescentsČlánok vyšiel v časopise
Czech-Slovak Pediatrics
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