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Phenotypic and Molecular Characteristics of Children with Progressive Familial Intrahepatic Cholestasis in South China

PURPOSE: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. METHODS: We collected and analyzed relevant data related to...

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Autores principales: Zhang, Wen, Lin, Ruizhu, Lu, Zhikun, Sheng, Huiying, Xu, Yi, Li, Xiuzhen, Cheng, Jing, Cai, Yanna, Mao, Xiaojian, Liu, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667226/
https://www.ncbi.nlm.nih.gov/pubmed/33215027
http://dx.doi.org/10.5223/pghn.2020.23.6.558
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author Zhang, Wen
Lin, Ruizhu
Lu, Zhikun
Sheng, Huiying
Xu, Yi
Li, Xiuzhen
Cheng, Jing
Cai, Yanna
Mao, Xiaojian
Liu, Li
author_facet Zhang, Wen
Lin, Ruizhu
Lu, Zhikun
Sheng, Huiying
Xu, Yi
Li, Xiuzhen
Cheng, Jing
Cai, Yanna
Mao, Xiaojian
Liu, Li
author_sort Zhang, Wen
collection PubMed
description PURPOSE: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. METHODS: We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. RESULTS: Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. CONCLUSION: The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.
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spelling pubmed-76672262020-11-18 Phenotypic and Molecular Characteristics of Children with Progressive Familial Intrahepatic Cholestasis in South China Zhang, Wen Lin, Ruizhu Lu, Zhikun Sheng, Huiying Xu, Yi Li, Xiuzhen Cheng, Jing Cai, Yanna Mao, Xiaojian Liu, Li Pediatr Gastroenterol Hepatol Nutr Original Article PURPOSE: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. METHODS: We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. RESULTS: Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. CONCLUSION: The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease. The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition 2020-11 2020-11-05 /pmc/articles/PMC7667226/ /pubmed/33215027 http://dx.doi.org/10.5223/pghn.2020.23.6.558 Text en Copyright © 2020 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Zhang, Wen
Lin, Ruizhu
Lu, Zhikun
Sheng, Huiying
Xu, Yi
Li, Xiuzhen
Cheng, Jing
Cai, Yanna
Mao, Xiaojian
Liu, Li
Phenotypic and Molecular Characteristics of Children with Progressive Familial Intrahepatic Cholestasis in South China
title Phenotypic and Molecular Characteristics of Children with Progressive Familial Intrahepatic Cholestasis in South China
title_full Phenotypic and Molecular Characteristics of Children with Progressive Familial Intrahepatic Cholestasis in South China
title_fullStr Phenotypic and Molecular Characteristics of Children with Progressive Familial Intrahepatic Cholestasis in South China
title_full_unstemmed Phenotypic and Molecular Characteristics of Children with Progressive Familial Intrahepatic Cholestasis in South China
title_short Phenotypic and Molecular Characteristics of Children with Progressive Familial Intrahepatic Cholestasis in South China
title_sort phenotypic and molecular characteristics of children with progressive familial intrahepatic cholestasis in south china
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667226/
https://www.ncbi.nlm.nih.gov/pubmed/33215027
http://dx.doi.org/10.5223/pghn.2020.23.6.558
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