Abstract
BackgroundBerardinelli-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.ResultsAnalysis 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.ConclusionsOur study largely enhances the current knowledge of phenotypic and genotypic heterogeneity of BSCL and promotes the more comprehensive understanding of pathogenic mechanisms for BSCL.
Highlights
Berardinelli-Seip congenital lipodystrophy (BSCL) is a heterogeneous autosomal recessive disorder characterized by an almost total lack of adipose tissue in the body
Since the mutations in CAV1 or PTRF concern a minority of patients and the alterations in AGPAT2 or BSCL2 are responsible for the majority of BSCL cases [23],our study was only focused on those cases with mutations on AGPAT2 and BSCL2 to perform genotype-phenotype analyses (Supplementary Table 1) [3, 8, 12, 20, 23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52]
Data presentation A total of 341 patients with different racial background were retrieved from 60 BSCL-related studies: BSCL type I (AGPAT2) n = 83, type II (BSCL2) n = 168, type III (CAV1) n = 1, type IV (PTRF) n = 26, patients with unknown genotype n = 62, and only one patient with mutations in both BSCL2 and PTRF [16]
Summary
Berardinelli-Seip congenital lipodystrophy (BSCL) is a heterogeneous autosomal recessive disorder characterized by an almost total lack of adipose tissue in the body. We retrieved 341 cases from 60 BSCL-related studies worldwide and aimed to explore genotypephenotype correlations based on mutations of AGPAT2 and BSCL2 genes from 251 cases. We inferred new candidate genes for BSCL through protein-protein interaction and phenotype-similarity. Because whole body fat tissue lacks the ability to store fat, fat is enriched in the heart, liver and other organs [3]. This may lead to severe consequences such as diabetes mellitus, cardiomyopathy, hepatopathy, acanthosis nigricans and intellectual disability [4, 5]. No conclusion has been made whether there is a gender difference in the prevalence of phenotypes shared by male and female patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
