Severe cardiac phenotype of Berardinelli-Seip congenital lipodystrophy in an infant with homozygous E189X BSCL2 mutation

Department of Paediatrics, “Germans Trias i Pujol” Hospital, Badalona, Autonomous University of Barcelona, Spain
European journal of medical genetics (Impact Factor: 1.47). 01/2009; 52(1):14-16. DOI: 10.1016/j.ejmg.2008.10.006
Source: PubMed


Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive condition associating insulin resistance, absence of subcutaneous fat and muscular hypertrophy. Disease-causing mutations have been described in AGPAT2 and BSCL2 genes. Hypertrophic cardiomyopathy is a classical late (third decade) complication which has only been occasionally described in childhood. We report on a 4-month-old Chinese male infant who presented with a severe BSCL “cardiac” phenotype comprising heart failure, hypertension and hypertrophic cardiomyopathy.

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    • "Specifically, Berardinelli–Seip congenital lipodystrophy is a condition associating insulin resistance, absence of subcutaneous fat, AN, and muscular hypertrophy caused by mutation in either AGPAT2 (OMIM#603100) or BSCL2 (OMIM# 606158) (Friguls et al. 2009; Miranda et al. 2009), AN associating with severe skeletal dysplasias due to activating mutations in FGFR3 (OMIM#134934) (Alatzoglou et al. "
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    • "Early onset diabetes mellitus present in our patients were comparable with homozygous nonsense mutations identified in Chinese and severe insulin resistance in Japanese and Brazilian patients [9,14,15], however we did not perform the insulin resistance test in our patients. The hypertrophic cardiomyopathy identified in our cases was less severe as compared to Chinese patient caused by homozygous nonsense mutation [17]. There was mild mental retardation (IQ score 65–75) in both of our patients but the brain MRI did not reveal brain atrophy. "
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    ABSTRACT: Congenital generalized lipodystrophy (CGL) also known as Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a genetically heterogeneous disorder characterized by loss of adipose tissues, Acanthosis nigricans, diabetes mellitus, muscular hypertrophy, hepatomegaly and hypertriglyceridemia. There are four subclinical phenotypes of CGL (CGL1-4) and mutations in four genes AGPAT2, BSCL2, CAV1 and PTRF have been assigned to each type. The study included clinical and molecular investigations of CGL disease in a consanguineous Pakistani family. For mutation screening all the coding exons including splice junctions of AGPAT2, BSCL2, CAV1 and PTRF genes were PCR amplified and sequenced directly using an automated DNA sequencer ABI3730. Sequence analysis revealed a single base pair deletion mutation (c.636delC; p.Tyr213ThrfsX20) in exon 5 of BSCL2 gene causing a frame shift and premature termination codon. Mutation identified here in BSCL2 gene causing congenital generalized lipodystrophy is the first report in Pakistani population. The patients exhibited characteristic features of generalized lipodystrophy, Acanthosis nigricans, diabetes mellitus and hypertrophic cardiomyopathy. Virtual Slides The virtual slide(s) for this article can be found here:
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