Two unrelated patients with rare Crigler-Najjar syndrome type I: two novel mutations and a patient with loss of heterozygosity of UGT1A1 gene

Li, Yan; Qu, Yu-jin; Zhong, Xuemei; Cao, Yunxia; Jin, Limin; Bai, Jin-li; Ma, Xiaojing; Jin, Yu-wei; Wang, Hong; Zhang, Yanling; Song, Fang

doi:10.1631/jzus.b1300233

Cited by 5 publications

(3 citation statements)

References 15 publications

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“…Nine of the 11 cases carried variations that are reported here for the first time in CNS-II patients (patients 3 to 11). The two variants predicted to cause truncation of UGT (M418fsX423 variant and Q239X variant) were also previously detected in CNS-I patients [ 13 , 14 ]. The Y486D variant has been shown to lower the bilirubin UGT activity by more than 90% [ 15 ] and was detected only in CNS-II patients.…”

Section: Discussionmentioning

confidence: 98%

Spectrum of UGT1A1 Variations in Chinese Patients with Crigler-Najjar Syndrome Type II

Deng

Mao

2015

PLoS ONE

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Crigler–Najjar Syndrome type II (CNS-II) is an autosomal recessive hereditary condition of unconjugated hyperbilirubinemia without hemolysis, with bilirubin levels ranging from 102.6 μmol/L to 342 μmol/L. CNS-II is caused by a deficiency of UDP-glucuronyl transferase (UGT), which is encoded by the UDP-glucuronyl transferase 1A1 gene (UGT1A1). In East Asian populations, the compound homozygous UGT1A1 G71R and Y486D variants are frequently observed in cases with bilirubin levels exceeding 200 μmol/L. In this study, we investigated the spectrum of UGT1A1 variations in Chinese CNS-II patients. We sequenced the enhancer, promoter, and coding regions of UGT1A1 in 11 unrelated Chinese CNS-II patients and 80 healthy controls. Nine of these patients carried variations that are here reported for the first time in CNS-II patients, although they have been previously reported for other types of hereditary unconjugated hyperbilirubinemia. These individual variations have less influence on UGT activity than do the compound homozygous variation (combination of homozygous G71R variant and Y486D variant). Therefore, we propose that the spectrum of UGT1A1 variations in CNS-II differs according to the bilirubin levels.

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Section: Discussionmentioning

confidence: 98%

Spectrum of UGT1A1 Variations in Chinese Patients with Crigler-Najjar Syndrome Type II

Deng

Mao

2015

PLoS ONE

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“…The 'homozygous mutation' of c.1253delT in exon 4 of the UGT1A1 gene was detected in the patient by DNA sequencing in our previous study ( 12 ). The same mutation was observed in his father, but not in his mother.…”

Section: Resultsmentioning

confidence: 65%

“…His total serum bilirubin level was 520.6 µ mol/l and serum unconjugated bilirubin level was 499.6 µ mol/l. The patient succumbed to kernicterus at 13 months of age, due to molecularly confirmed CN-I syndrome ( 12 ). However, upon reviewing the related medical records, other abnormal manifestations in the patient that could not be fully attributed to CN-I alone, were identified.…”

Section: Resultsmentioning

confidence: 99%

X-linked ichthyosis and Crigler-Najjar syndrome I: Coexistence in a male patient with two copy number variable regions of 2q37.1 and Xp22.3

Bai

Cao

et al. 2015

Molecular Medicine Reports

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X-linked ichthyosis (XLI) is an X-linked recessive skin disorder generally restricted to males, which arises from mutations in the steroid sulfatase (STS) gene located on Xp22.3. Crigler-Najjar syndrome (CN-I) is a rare autosomal recessive disease caused by the homozygous or compound heterozygous mutations in the UPD-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) gene on chromosome 2q37. A male patient was referred to the Department of Medical Genetics with of severe icterus and ichthyosis. The patient and his family members underwent genetic tests related to XLI and CN-I. Quantitative polymerase chain reaction on genomic DNA was performed to determine the gene copy number, while single nucleotide polymorphism array analysis was conducted to identify deletion mutations. Family pedigree analysis showed that the patient and his two cousins were all affected by ichthyosis, which was in accordance with the inheritance pattern of an X-linked recessive disease. In addition, the patient's serum bilirubin concentration (>340 mmol/l) was markedly greater than the normal level. The patient presented with kernicterus and phenobarbital treatment was ineffective. The clinical diagnosis of XLI was confirmed molecularly by laboratory evidence of a maternal 1.61 M deletion (including the STS gene) on ChrXp22.31. Coincidentally, the male patient was also confirmed to carry a rare maternal inherited microdeletion (374 Kb) comprising the entire UGT1A1 gene combined with a paternal UGT1A1 mutation (c.1253delT), a causative event of CN-I. To the best of our knowledge, this study reported for the first time the comorbidity of XLI and CN-I in a male patient. The results suggested that co-occurrence of these two recessive diseases in a patient may be incidental.

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A novel deletion with two pathogenic variants of UGT1A1 causing Crigler-Najjar syndrome in two unrelated Chinese

Yang

Zhou

et al. 2019

Clinical Biochemistry

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Two unrelated patients with rare Crigler-Najjar syndrome type I: two novel mutations and a patient with loss of heterozygosity of UGT1A1 gene

Cited by 5 publications

References 15 publications

Spectrum of UGT1A1 Variations in Chinese Patients with Crigler-Najjar Syndrome Type II

Spectrum of UGT1A1 Variations in Chinese Patients with Crigler-Najjar Syndrome Type II

X-linked ichthyosis and Crigler-Najjar syndrome I: Coexistence in a male patient with two copy number variable regions of 2q37.1 and Xp22.3

A novel deletion with two pathogenic variants of UGT1A1 causing Crigler-Najjar syndrome in two unrelated Chinese

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