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Genotype-phenotype correlations of Berardinelli-Seip congenital lipodystrophy and novel candidate genes prediction
BACKGROUND: Berardinelli-Seip congenital lipodystrophy (BSCL) is a heterogeneous autosomal recessive disorder characterized by an almost total lack of adipose tissue in the body. Mutations in the AGPAT2, BSCL2, CAV1 and PTRF genes define I-IV subtype of BSLC respectively and clinical data indicate t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191718/ https://www.ncbi.nlm.nih.gov/pubmed/32349771 http://dx.doi.org/10.1186/s13023-020-01383-y |
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author | Ren, Meng Shi, Jingru Jia, Jinmeng Guo, Yongli Ni, Xin Shi, Tieliu |
author_facet | Ren, Meng Shi, Jingru Jia, Jinmeng Guo, Yongli Ni, Xin Shi, Tieliu |
author_sort | Ren, Meng |
collection | PubMed |
description | BACKGROUND: Berardinelli-Seip congenital lipodystrophy (BSCL) is a heterogeneous autosomal recessive disorder characterized by an almost total lack of adipose tissue in the body. Mutations in the AGPAT2, BSCL2, CAV1 and PTRF genes define I-IV subtype of BSLC respectively and clinical data indicate that new causative genes remain to be discovered. Here, we retrieved 341 cases from 60 BSCL-related studies worldwide and aimed to explore genotype-phenotype correlations based on mutations of AGPAT2 and BSCL2 genes from 251 cases. We also inferred new candidate genes for BSCL through protein-protein interaction and phenotype-similarity. RESULTS: Analysis results show that BSCL type II with earlier age of onset of diabetes mellitus, higher risk to suffer from premature death and mental retardation, is a more severe disorder than BSCL type I, but BSCL type I patients are more likely to have bone cysts. In BSCL type I, females are at higher risk of developing diabetes mellitus and acanthosis nigricans than males, while in BSCL type II, males suffer from diabetes mellitus earlier than females. In addition, some significant correlations among BSCL-related phenotypes were identified. New candidate genes prediction through protein-protein interaction and phenotype-similarity was conducted and we found that CAV3, EBP, SNAP29, HK1, CHRM3, OBSL1 and DNAJC13 genes could be the pathogenic factors for BSCL. Particularly, CAV3 and EBP could be high-priority candidate genes contributing to pathogenesis of BSCL. CONCLUSIONS: Our study largely enhances the current knowledge of phenotypic and genotypic heterogeneity of BSCL and promotes the more comprehensive understanding of pathogenic mechanisms for BSCL. |
format | Online Article Text |
id | pubmed-7191718 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-71917182020-05-04 Genotype-phenotype correlations of Berardinelli-Seip congenital lipodystrophy and novel candidate genes prediction Ren, Meng Shi, Jingru Jia, Jinmeng Guo, Yongli Ni, Xin Shi, Tieliu Orphanet J Rare Dis Research BACKGROUND: Berardinelli-Seip congenital lipodystrophy (BSCL) is a heterogeneous autosomal recessive disorder characterized by an almost total lack of adipose tissue in the body. Mutations in the AGPAT2, BSCL2, CAV1 and PTRF genes define I-IV subtype of BSLC respectively and clinical data indicate that new causative genes remain to be discovered. Here, we retrieved 341 cases from 60 BSCL-related studies worldwide and aimed to explore genotype-phenotype correlations based on mutations of AGPAT2 and BSCL2 genes from 251 cases. We also inferred new candidate genes for BSCL through protein-protein interaction and phenotype-similarity. RESULTS: Analysis results show that BSCL type II with earlier age of onset of diabetes mellitus, higher risk to suffer from premature death and mental retardation, is a more severe disorder than BSCL type I, but BSCL type I patients are more likely to have bone cysts. In BSCL type I, females are at higher risk of developing diabetes mellitus and acanthosis nigricans than males, while in BSCL type II, males suffer from diabetes mellitus earlier than females. In addition, some significant correlations among BSCL-related phenotypes were identified. New candidate genes prediction through protein-protein interaction and phenotype-similarity was conducted and we found that CAV3, EBP, SNAP29, HK1, CHRM3, OBSL1 and DNAJC13 genes could be the pathogenic factors for BSCL. Particularly, CAV3 and EBP could be high-priority candidate genes contributing to pathogenesis of BSCL. CONCLUSIONS: Our study largely enhances the current knowledge of phenotypic and genotypic heterogeneity of BSCL and promotes the more comprehensive understanding of pathogenic mechanisms for BSCL. BioMed Central 2020-04-29 /pmc/articles/PMC7191718/ /pubmed/32349771 http://dx.doi.org/10.1186/s13023-020-01383-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Ren, Meng Shi, Jingru Jia, Jinmeng Guo, Yongli Ni, Xin Shi, Tieliu Genotype-phenotype correlations of Berardinelli-Seip congenital lipodystrophy and novel candidate genes prediction |
title | Genotype-phenotype correlations of Berardinelli-Seip congenital lipodystrophy and novel candidate genes prediction |
title_full | Genotype-phenotype correlations of Berardinelli-Seip congenital lipodystrophy and novel candidate genes prediction |
title_fullStr | Genotype-phenotype correlations of Berardinelli-Seip congenital lipodystrophy and novel candidate genes prediction |
title_full_unstemmed | Genotype-phenotype correlations of Berardinelli-Seip congenital lipodystrophy and novel candidate genes prediction |
title_short | Genotype-phenotype correlations of Berardinelli-Seip congenital lipodystrophy and novel candidate genes prediction |
title_sort | genotype-phenotype correlations of berardinelli-seip congenital lipodystrophy and novel candidate genes prediction |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191718/ https://www.ncbi.nlm.nih.gov/pubmed/32349771 http://dx.doi.org/10.1186/s13023-020-01383-y |
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