Inheritance of type 2 Crigler-Najjar hyperbilirubinaemia

Hunter, John; Thompson, R. P. H.; Dunn, P M; Williams, Roger

doi:10.1136/gut.14.1.46

Cited by 36 publications

(15 citation statements)

References 16 publications

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“…The mutation from patient B causes a 10-fold increase in the apparent Km for bilirubin when compared to expressed B-UGTI or human liver microsomes. (2)(3)(4)(5)(6)(7)(8)(9)(10). Phenobarbital response varies between 27 and 78% and serum bilirubin levels can vary between 340 and 100 1iM.…”

Section: Resultsmentioning

confidence: 99%

“…The disease is caused by an absence or strong reduction of the activity of the hepatic enzyme bilirubin UDPglucuronosyltransferase (B-UGT) (EC 2.4.1.17). The CN syndrome can be divided into two subtypes; the more severe type I with high levels of serum bilirubin and the milder type II with lower levels of serum bilirubin and a reduction of these levels of more than 30% upon phenobarbital treatment (2)(3)(4)(5)(6)(7)(8)(9)(10). Bile of type II patients contains bilirubin glucuronides, though much less than bile of healthy controls (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

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Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase.

Bosma²,

et al. 1994

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Crigler-Najjar (CN) Kinetic constants for the glucuronidation of bilirubin were determined. The affinities for bilirubin of B-UGT1 expressed in COS cells and B-UGT from human liver microsomes were similar with Km of 5.1±0.9 ,uM and 7.9±5.3 ,uM, respectively. B-UGT1 from patient B had a tenfold decreased affinity for bilirubin, Km = 56±23 ,LM.At physiological concentrations of bilirubin both type II patients will have a strongly reduced conjugation capacity, whereas type I patients have no B-UGT activity. We conclude that CN type I is caused by a complete absence of functional B-UGT and that in CN type II B-UGT activity is reduced. (J. Clin. Invest. 1994Invest. .94:2385Invest. -2391

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase.

Bosma²,

et al. 1994

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“…Based on pedigree analysis, the inheritance of CN type II has been postulated to be autosomal recessive (Blaschke et al 1974;Hunter et al 1973) or autosomal dominant with incomplete penetrance (Arias et al 1969). Gene analyses have shown both patients having recessive traits with homozygous missense mutations and a patient having dominant traits with a heterozygous nonsense mutation (Aono et al 1993;Bosma et al 1993;Koiwai et al 1996).…”

Section: Discussionmentioning

confidence: 99%

Analysis of bilirubin uridine 5′-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II

et al. 1998

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Crigler-Najjar syndrome (CN) type II is caused by a reduction in hepatic bilirubin uridine 5Ј-diphosphate (UDP)-glucuronosyltransferase activity. Recently, there has been progress in mutation analysis of patients with CN type II. Here, we analyzed both the coding and the promoter regions of the gene in seven Japanese patients with CN type II from five unrelated families. The mutations found in this study were classified into three types. The first type was composed of double homozygous missense mutations (Gly71Arg and Tyr486Asp) in exons 1 and 5. These mutations, which were detected in five patients from three unrelated families, were the commonest. The second type, which was detected in one patient, consisted of a single homozygous missense mutation (Arg209Trp) in exon 1. The third type, which was detected in one patient and was a new type of mutation combination, was composed of a homozygous insertion mutation of the TATAA element and a heterozygous missense mutation (Pro229Gln) in exon 1. Although the first and the second type of mutations are recessive, the third type appears to be dominant with incomplete penetrance, since the allele frequency of the insertion mutation of the TATAA element is very high (40%).

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“…The hereditary transmission of the disease would be autosomal and dominant [3]. However, Hunter et al [26] recently discussed this point and suggested that the disease would be due to the transmission of two abnormal genes, one from each parent. Each one of these two genes would regulate a different stage of the UCB metabolism.…”

Section: Introductionmentioning

confidence: 99%

Bilirubin and Paranitrophenol Glucuronyl Transferase Activities of the Liver in Patients with Gilbert’s Syndrome. An Attempt at a Biochemical Breakdown of the Gilbert’s Syndrome

Auclair¹,

Hakim²,

Boivin³

et al. 1976

Enzyme

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Hepatic bilirubin (Bil-GT) and paranitrophenol glucuronyl transferase (PNP-GT) activities were measured in 26 subjects with Gilbert’s syndrome (GS) and in one subject with a Crigler-Najjar type 2. Firstly, the results allowed us to distinguish three groups of patients in GS. In the first group, Bil-GT activity decreased by 25% of that of the controls and PNP-GT activity was normal. In the second group, Bil-GT decreased by 25% of that of the controls and PNP-GT decreased by 50% of that of the controls. In the third group, Bil-GT decreased by 50% of that of the controls and PNP-GT activity was normal. Secondly, the results showed in the Crigler-Najjar type 2 that Bil-GT activity was 25% of that of the controls and PNP-GT was 10% of that of the controls. From these results the following hypothesis has been raised: (1) the subjects of the third GS group were probably heterozygous to the homozygous disease which affected the subjects of the first GS group, and (2) the subjects of the second GS group were most likely heterozygous to the homozygous disease which affected our Crigler-Najjar type 2. However, in the present state of our knowledge, the scheme of GS classification which we propose requires confirmation.

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Inheritance of type 2 Crigler-Najjar hyperbilirubinaemia

Cited by 36 publications

References 16 publications

Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase.

Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase.

Analysis of bilirubin uridine 5′-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II

Bilirubin and Paranitrophenol Glucuronyl Transferase Activities of the Liver in Patients with Gilbert’s Syndrome. An Attempt at a Biochemical Breakdown of the Gilbert’s Syndrome

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