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Front Surg 2022 27;9:889753. Epub 2022 Apr 27.

Department of Chest Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.

Background: Crigler-Najjar syndrome type 2 (CNS-II) is a rare genetic disease that is associated with a lack of uridine diphosphate-glucuronosyltransferase. Esophageal carcinoma is the sixth most common cause of cancer-related death worldwide, for which surgery is the most effective treatment. Reports on patients with both conditions requiring surgery are limited and The impact of hyperbilirubinemia caused by CNS-II on the perioperative period is unknown. Read More

J Clin Lab Anal 2022 Jun 9;36(6):e24482. Epub 2022 May 9.

Genomics of Signalopathies at the service of Medicine, Medical University of Sfax, Sfax, Tunisia.

Background: Uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1), which is the major UGT1 gene product, is located on chromosome 2q37. The expression of UGT1A1 is relatively managed by a polymorphic dinucleotide repeat inside the promoter TATA box consisting of 5-8 copies of a TA repeat. A (TA) 6TAA is considered as the wild type. Read More

Ital J Pediatr 2022 Apr 18;48(1):59. Epub 2022 Apr 18.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Pediatric Liver Unit, Milan, Italy.

Background: Several mutations of bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1) have been reported in patients with unconjugated hyperbilirubinemia. Few reports are available about the p.Pro364Leu mutation (P364L, c. Read More

Mol Genet Genomic Med 2022 Apr 14:e1958. Epub 2022 Apr 14.

Research Laboratory of Clinical Virology, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Genetic testing of UGT1A1 was used to facilitate the diagnosis of Gilbert syndrome, and analyze the distribution features of pathogenic variants in the Chinese population.

Methods: DNA was extracted from whole blood samples of patients with unconjugated hyperbilirubinemia, and sequencing of the UGT1A1 gene was performed after PCR amplification. After alignment with reference sequences, the known pathogenic variants were identified, the variant spectrum was analyzed, and the pathogenicity of novel variants was predicted using online mutation prediction tools. Read More

Liver Int 2022 Jul 29;42(7):1593-1604. Epub 2022 Mar 29.

Department of Gastroenterology & Hepatology and Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology & Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands.

Am J Med Genet A 2022 06 24;188(6):1848-1852. Epub 2022 Feb 24.

Department of Pediatrics, Chair of Pediatrics Jagiellonian University Medical College, Krakow, Poland.

This is the first report of the concurrent development of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and Crigler-Najjar syndrome type 1 (CNs1) inherited via uniparental disomy of chromosome 2, which are both autosomal recessive pathologies. Through an expanded newborn metabolic panel, a male infant was identified as having an acylcarnitine pattern typical for LCHADD, later confirmed to be caused by a well-characterized pathogenic variant in the HADHA gene located at 2p23. Prolonged non-hematologic jaundice requiring repetitive phototherapy prompted further genetic analysis, leading to the identification of another genetic abnormality consistent with CNs1, which was caused by a novel pathogenic variant in the UGT1A1 gene located at 2q37. Read More

J Child Neurol 2022 02 27;37(2):119-126. Epub 2021 Dec 27.

Department of Diagnostic Radiology, Mansoura Faculty of Medicine, Mansoura, Egypt.

Aim: To evaluate the role of diffusion tensor imaging of the auditory pathway in patients with Crigler Najjar syndrome type I and its relation to auditory brainstem response.

Methods: Prospective study was done including 12 patients with Crigler Najjar syndrome type I and 10 age- and sex-matched controls that underwent diffusion tensor imaging of brain. Mean diffusivity and fractional anisotropy at 4 regions of the brain and brainstem on each side were measured and correlated with the results of auditory brainstem response for patients. Read More

Drug Metab Rev 2022 02 22;54(1):1-21. Epub 2021 Nov 22.

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China.

UDP-glucuronyltransferase 1A1 (UGT1A1) is a member of the Phase II metabolic enzyme family and the only enzyme that can metabolize detoxified bilirubin. Inactivation and very low activity of UGT1A1 in the liver can be fatal or lead to lifelong Gilbert's syndrome (GS) and Crigler-Najjar syndrome (CN). To date, more than one hundred UGT1A1 polymorphisms have been discovered. Read More

Front Cardiovasc Med 2021 5;8:738798. Epub 2021 Oct 5.

Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Egypt.

Arkh Patol 2021 ;83(5):27-30

Pediatric Gastroenterology and Hepatology Research Center of the Zabol university of Medical Sciences, Zabol, Iran.

Background. Crigler-Najjar syndrome (CNS) is a rare genetic disorder found in less than 1 per 1.000. Read More

Mol Genet Genomic Med 2021 11 21;9(11):e1805. Epub 2021 Sep 21.

Gastroenterohepatology Research Center, Nemazee Teaching Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.

Med Pharm Rep 2021 Aug 10;94(Suppl No 1):S64-S67. Epub 2021 Aug 10.

Department of Internal Medicine, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, Republic of Moldova.

Crigler-Najjar syndrome is a rare autosomal recessive inherited non-hemolytic unconjugated hyperbilirubinemia caused by UDP-glucuronosyltransferase deficiency. There are two forms of this disorder. Type 1 disease is associated with severe jaundice and neurologic impairment due to bilirubin encephalopathy that can result in permanent neurologic sequelae. Read More

Front Cardiovasc Med 2021 22;8:685835. Epub 2021 Jul 22.

Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

J Clin Transl Hepatol 2021 Apr 11;9(2):180-186. Epub 2021 Mar 11.

Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You'an Hospital Affiliated to Capital Medical University, Beijing, China.

Background And Aims: Bilirubin encephalopathy/kernicterus is very rare in adults. This study is aimed to investigate the clinical manifestations and genetic features of two patients with -related kernicterus.

Methods: Sanger sequencing analysis was performed to identify gene mutations in the patients and their families. Read More

Case Rep Gastroenterol 2021 Jan-Apr;15(1):296-304. Epub 2021 Mar 11.

General and HPB Surgery, Al Assad University Hospital, Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic.

Liver transplantation (LT) is the only curative therapy for the end-stage liver diseases and some metabolic disorders which affect the hepatic cell like the Crigler-Najjar syndrome type 1 (CNSI). Although the LT is a routine procedure in many centers worldwide, the postoperative complications such as rejection, arterial thrombosis, and infection remain serious challenges even in big centers. In our paper, we demonstrate the first two LTs in Syria. Read More

Cureus 2021 Jan 12;13(1):e12669. Epub 2021 Jan 12.

Internal Medicine, Services Institute of Medical Sciences, Lahore, PAK.

Crigler-Najjar syndrome is an inborn error of metabolism caused by a point mutation in one of the five exons of UGT1A1 gene, the product of which is responsible for elimination of bilirubin via bile. A number of hyperbilirubinemia disorders similar to Crigler-Najjar syndrome are reported, but they differ in their level of unconjugated bilirubin and responses to the treatment. Here we report a 14-year-old male patient admitted to hospital with the complaint of vomiting and frequent tonsillitis. Read More

Clin Transplant 2021 04 22;35(4):e14219. Epub 2021 Feb 22.

Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Introduction: Crigler-Najjar syndrome (CNS) is a rare inherited disorder that is characterized by high levels of non-hemolytic, unconjugated hyperbilirubinemia leading to brain damage and even death. Liver transplantation (LT) can correct the metabolic defect, but there are little data regarding LT in this patient cohort. The liver parenchyma has been considered to be structurally normal in CNS, but there is growing evidence of clinically silent but histologically significant fibrosis in CNS patients. Read More

Mol Ther Methods Clin Dev 2021 Mar 3;20:287-297. Epub 2020 Dec 3.

Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, AGEM, Meibergdreef 69-71, 1105 BK Amsterdam, the Netherlands.

A clinical trial using adeno-associated virus serotype 8 (AAV8)-human uridine diphosphate glucuronosyltransferase 1A1 (h) to treat inherited severe unconjugated hyperbilirubinemia (Crigler-Najjar syndrome) is ongoing, but preclinical data suggest that long-term efficacy in children is impaired due to loss of transgene expression upon hepatocyte proliferation in a growing liver. This study aims to determine at what age long-term efficacy can be obtained in the relevant animal model and whether immune modulation allows re-treatment using the same AAV vector. Neonatal, suckling, and juvenile Ugt1a1-deficient rats received a clinically relevant dose of AAV8-h, and serum bilirubin levels and anti-AAV8 neutralizing antibodies (NAbs) in serum were monitored. Read More

Stem Cell Res 2021 03 12;51:102167. Epub 2021 Jan 12.

Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address:

Human fibroblasts cells from a Crigler-Najjar Syndrome (CNS) patient were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids expressing OCT4, SOX2, NANOG, KLF4, c-MYC and LIN28. The derived CNS705-iPSC line is homozygous for the UGT1A1 c.877_890delTACATTAATGCTTCinsA mutation. Read More

Eur J Med Genet 2021 Feb 7;64(2):104139. Epub 2021 Jan 7.

Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire d'Hématologie Moléculaire et Cellulaire, Tunisie.

Introduction: Unconjugated hyperbilirubinemia (UCB) is a feature of Gilbert's syndrome (GS) and Crigler-Najjar's syndrome (CNS), which are two hereditary defects in bilirubin metabolism. Both syndromes are linked to mutations in the UGT1A1 gene, which cause either the decrease or the absence of the UGT1A1 enzymatic activity. Here, we investigated the molecular basis of the UGT1A1 gene in Tunisian patients presenting with unconjugated hyperbilirubinemia. Read More

Niger J Clin Pract 2020 Dec;23(12):1772-1775

Department of Anesthesiology, University of Health Sciences, Gazi Yasargil Diyarbakir Training and Research Hospital, Diyarbakir, Turkey.

Crigler-Najjar syndrome is a rare disease which is associated with congenital deficiency of uridine-diphosphate-gulukronyltransferase (UDP-glucuronosyltransferase, UGT) enzyme. In the surgery of these patients, it is necessary to use an anesthetic method that causes less damage to the liver. Spinal anesthesia is a good alternative to general anesthesia in these patients. Read More

Int J Organ Transplant Med 2020 ;11(1):15-25

Transplant Research Center, Shiraz University of Medical Sciences.

Background: Hepatocyte transplantation using isolated human hepatocytes is an alternative source that can be used for the treatment of metabolic diseases and acute liver failure as a time bridge to liver transplantation. These cells can also be used for bioartificial liver systems and study of drug toxicity.

Objective: To determine which cold preservation solution is better maintain the liver function. Read More

JGH Open 2020 Oct 16;4(5):1009-1011. Epub 2020 May 16.

Department of Liver Disease, The Second Hospital of Nanjing Nanjing University of Chinese Medicine Nanjing China.

Crigler-Najjar syndrome (CNs) is a rare hereditary unconjugated hyperbilirubinemia caused by mutations in the bilirubin Uridine (UDP) glucuronosyltransferase family 1 member A1 (UGT1A1, ENSG00000241635) gene. Two patients were clinically diagnosed with Crigler-Najjar Syndrome types II (CNs-II) can be clinically diagnosed which were based on the level of total bilirubin, efficacy of phenobarbital treatment, normal liver architecture and exclusion of hemolysis. Diagnosis was also confirmed by UGT1A1 gene mutations, which by sequencing the coding region for UGT1A1 gene mutations, which were the homozygous mutations c. Read More

Pediatr Surg Int 2020 Dec 10;36(12):1443-1450. Epub 2020 Oct 10.

Organ Transplantation Center, Tianjin First Central Hospital, No.24 Fukang Road, Nankai District, 300192, Tianjin, China.

Purpose: To investigate the efficacy of living donor liver transplantation (LDLT) plus domino-auxiliary partial orthotopic liver transplantation (D-APOLT) in pediatric patients with metabolic disorders.

Methods: From May 2017 to October 2018, two patients with ornithine aminotransferase deficiency (OTCD) and one patient with type I Crigler-Najjar syndrome (CNS1) received LDLT, their livers were prepared as donors for D-APOLT. Two patients with CNS1 received domino liver grafts from OTCD patients; one OTCD patient received a domino liver graft from a CNS1 patient. Read More

Spec Care Dentist 2020 Nov 3;40(6):611-612. Epub 2020 Sep 3.

Oral Medicine and Special Care Dentistry, School of Dentistry, The University of Jordan, Amman, Jordan.

J Pediatr Genet 2021 Dec 29;10(4):323-325. Epub 2020 Jul 29.

Department of Pediatrics, San Agustín University Hospital, Avilés, Spain.

In this article, we reported a patient with Crigler-Najjar syndrome type II with high-unconjugated bilirubin levels that decreased after phenobarbital treatment. The patient had two novel missense mutations in the gene and a promoter variant in one allele. One mutation was c. Read More

Mol Ther Methods Clin Dev 2020 Sep 3;18:250-258. Epub 2020 Jun 3.

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, AG&M, 1105 BK Amsterdam, the Netherlands.

Potency assessment of clinical-grade vector lots is crucial to support adeno-associated virus (AAV) vector release and is required for future marketing authorization. We have developed and validated a cell-based, quantitative potency assay that detects both transgenic expression and activity of an AAV8-h vector, which is currently under clinical evaluation for the treatment of Crigler-Najjar syndrome. Potency of AAV8-h was evaluated . Read More

Zhonghua Gan Zang Bing Za Zhi 2020 May;28(5):428-433

Difficult & Complicated Liver Diseases and Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069,China; Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Beijing 100069,China.

To investigate the mutation characteristics and clinical relevance of Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS) in relation to uridine diphosphate glucuronosyltransferase A1 (UGT1A1) gene. The characteristics of UGT1A1 gene mutation and their clinical relevance were analyzed by searching PubMed and Human Gene Mutation Databases. A total of 163 mutation sites were found in the UGT1A1 gene since November 16, 2018. Read More

Pediatr Res 2021 02 1;89(3):510-517. Epub 2020 May 1.

Section of Molecular Metabolism and Nutrition, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.

Background: Unconjugated hyperbilirubinemia, a feature of neonatal jaundice or Crigler-Najjar syndrome, can lead to neurotoxicity and even death. We previously demonstrated that unconjugated bilirubin (UCB) can be eliminated via transintestinal excretion in Gunn rats, a model of unconjugated hyperbilirubinemia, and that this is stimulated by enhancing fecal fatty acid excretion. Since transintestinal excretion also occurs for cholesterol (TICE), we hypothesized that increasing fecal cholesterol excretion and/or TICE could also enhance fecal UCB disposal and subsequently lower plasma UCB concentrations. Read More