Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

Genetic and biochemical study of dual hereditary jaundice: Dubin-Johnson and Gilbert's syndromes. Haplotyping and founder effect of deletion in ABCC2

L. Slachtova, O. Seda, J. Behunova, M. Mistrik, P. Martasek,

. 2016 ; 24 (5) : 704-9. [pub] 20150909

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

E-resources Online Full text

NLK Free Medical Journals from 2009
PubMed Central from 2009 to 1 year ago
Europe PubMed Central from 2009 to 1 year ago
ProQuest Central from 2000-01-01 to 1 year ago
Open Access Digital Library from 1998-01-01
Health & Medicine (ProQuest) from 2000-01-01 to 1 year ago

Dual hereditary jaundice, a combination of Dubin-Johnson and Gilbert's syndromes, is a rare clinical entity resulting from the compound defects of bilirubin conjugation and transport. We aimed to study the hereditary jaundice in 56 members from seven seemingly unrelated Roma families, to find the causal genetic defect and to estimate its origin in Roma population. On the basis of biochemical results of total and conjugated serum bilirubin and clinical observations, ABCC2 gene, TATA box and phenobarbital enhancer (PBREM) of UGT1A1 gene were analyzed by sequencing, RFLP and fragment analysis. We found a novel variant c.1013_1014delTG in the eighth exon of ABCC2 gene in 17 individuals in homozygous state. Dual defect NG_011798.1:c.[1013_1014delTG]; NG_002601.2:g.[175492_175493insTA] in homozygous state was found in four subjects. Biochemical analyses of porphyrins and coproporphyrin isomers in urine performed by HPLC showed inverted ratio of excreted coproporphyrin, with the predominance of coproporphyrin I (up to 100%), typical for patients with Dubin-Johnson syndrome. Pursuant cultural and social specifics of the population led us to suspect a founder effect; therefore, we performed a haplotype study using genotyping data from Affymetrix Genome-Wide Human SNP Array 6.0. As a result, we detected a common 86 kbp haplotype encompassing promoter and part of the ABCC2 coding region among all families, and estimated the age of the ancestral variant to 178-185 years. In this study, we found a novel deletion in ABCC2 gene, described genetic and biochemical features of dual hereditary jaundice and confirmed the existence of founder effect and common haplotype among seven Roma families.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc17001019
003      
CZ-PrNML
005      
20170116095332.0
007      
ta
008      
170103s2016 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1038/ejhg.2015.181 $2 doi
024    7_
$a 10.1038/ejhg.2015.181 $2 doi
035    __
$a (PubMed)26350512
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Slachtova, Lenka $u Department of Pediatrics, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
245    10
$a Genetic and biochemical study of dual hereditary jaundice: Dubin-Johnson and Gilbert's syndromes. Haplotyping and founder effect of deletion in ABCC2 / $c L. Slachtova, O. Seda, J. Behunova, M. Mistrik, P. Martasek,
520    9_
$a Dual hereditary jaundice, a combination of Dubin-Johnson and Gilbert's syndromes, is a rare clinical entity resulting from the compound defects of bilirubin conjugation and transport. We aimed to study the hereditary jaundice in 56 members from seven seemingly unrelated Roma families, to find the causal genetic defect and to estimate its origin in Roma population. On the basis of biochemical results of total and conjugated serum bilirubin and clinical observations, ABCC2 gene, TATA box and phenobarbital enhancer (PBREM) of UGT1A1 gene were analyzed by sequencing, RFLP and fragment analysis. We found a novel variant c.1013_1014delTG in the eighth exon of ABCC2 gene in 17 individuals in homozygous state. Dual defect NG_011798.1:c.[1013_1014delTG]; NG_002601.2:g.[175492_175493insTA] in homozygous state was found in four subjects. Biochemical analyses of porphyrins and coproporphyrin isomers in urine performed by HPLC showed inverted ratio of excreted coproporphyrin, with the predominance of coproporphyrin I (up to 100%), typical for patients with Dubin-Johnson syndrome. Pursuant cultural and social specifics of the population led us to suspect a founder effect; therefore, we performed a haplotype study using genotyping data from Affymetrix Genome-Wide Human SNP Array 6.0. As a result, we detected a common 86 kbp haplotype encompassing promoter and part of the ABCC2 coding region among all families, and estimated the age of the ancestral variant to 178-185 years. In this study, we found a novel deletion in ABCC2 gene, described genetic and biochemical features of dual hereditary jaundice and confirmed the existence of founder effect and common haplotype among seven Roma families.
650    _2
$a bilirubin $x metabolismus $7 D001663
650    _2
$a koproporfyriny $x moč $7 D003306
650    _2
$a ženské pohlaví $7 D005260
650    12
$a efekt zakladatele $7 D018703
650    12
$a delece genu $7 D017353
650    _2
$a Gilbertova nemoc $x diagnóza $x genetika $7 D005878
650    _2
$a glukuronosyltransferasa $x genetika $7 D014453
650    _2
$a haplotypy $7 D006239
650    _2
$a homozygot $7 D006720
650    _2
$a lidé $7 D006801
650    _2
$a žloutenka chronická idiopatická $x diagnóza $x genetika $7 D007566
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a proteiny spojené s mnohočetnou rezistencí k lékům $x genetika $7 D027425
650    _2
$a polymorfismus délky restrikčních fragmentů $7 D012150
650    _2
$a jednonukleotidový polymorfismus $7 D020641
650    _2
$a TATA box $7 D016385
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Seda, Ondrej $u Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
700    1_
$a Behunova, Jana $u Department of Pediatrics, P. J. Safarik University, Kosice, Vienna, Slovakia. Institute of Medical Genetics, University of Vienna, Vienna, Austria.
700    1_
$a Mistrik, Martin $u Department of Medical Genetics, Alpha Medical, Spisska Nova Ves, Slovakia.
700    1_
$a Martasek, Pavel $u Department of Pediatrics, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
773    0_
$w MED00005019 $t European journal of human genetics EJHG $x 1476-5438 $g Roč. 24, č. 5 (2016), s. 704-9
856    41
$u https://pubmed.ncbi.nlm.nih.gov/26350512 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20170103 $b ABA008
991    __
$a 20170116095436 $b ABA008
999    __
$a ok $b bmc $g 1180159 $s 961586
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2016 $b 24 $c 5 $d 704-9 $e 20150909 $i 1476-5438 $m European journal of human genetics $n Eur J Hum Genet $x MED00005019
LZP    __
$a Pubmed-20170103

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...