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

Friguls, Bibiana; Coroleu, Wifredo; Alcázar, Ricardo del; Hilbert, Pascale; Maldergem, Lionel Van; Pintos-Morell, Guillem

doi:10.1016/j.ejmg.2008.10.006

Cited by 29 publications

(32 citation statements)

References 15 publications

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“…While HCM is described in CGL type 2 (Agarwal et al 2003;Van Maldergem et al 2002), it is rarely present in the first months of life (Friguls et al 2009) as observed here. In addition, our patient is unusual since cardiac dimensions improved and even normalized.…”

Section: Discussionsupporting

confidence: 53%

A Patient with Congenital Generalized Lipodystrophy Due To a Novel Mutation in BSCL2: Indications for Secondary Mitochondrial Dysfunction

et al. 2011

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Background: Congenital generalized lipodystrophy (CGL) results from mutations in AGPAT2, encoding 1-acyl-glycerol-3-phosphate-acyltransferase 2 (CGL1; MIM 608594), BSCL2, encoding seipin (CGL2; MIM 269700), CAV1, encoding caveolin1 (CGL3; MIM 612526) or PTRF, encoding polymerase I and transcript release factor (CGL4; MIM 613327). This study aims to investigate the genotype/phenotype relationship and search for a possible pathogenic mechanism in a patient with CGL.Design: Case report. Patients and Setting: A 7-day-old child of consanguineous Turkish parents presented with a generalized loss of subcutaneous fat. He had a strikingly enlarged liver, high serum triglycerides, and hyperglycaemia, suggestive for CGL.Results: A novel homozygous mutation in the acceptor splice site of exon 5 of the BSCL2 gene was found in the genome of the proband. This mutation causes a complex RNA splicing defect and results in two different aberrant seipin proteins, which were normally expressed and localized to the endoplasmic reticulum like wild type protein. Analysis of the patient's urine showed intermittent elevations of citric acid intermediates and persistently high concentrations of ethylmalonic acid, suggestive of a disturbance of the mitochondrial respiratory chain.Conclusion: Here we report abnormal urinary organic acid levels, indicative of mitochondrial dysfunction, in a patient with CGL resulting from a novel mutation in BSCL2. Our findings suggest for the first time an association between CGL and secondary mitochondrial dysfunction.

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Section: Discussionsupporting

confidence: 53%

A Patient with Congenital Generalized Lipodystrophy Due To a Novel Mutation in BSCL2: Indications for Secondary Mitochondrial Dysfunction

et al. 2011

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“…The unusual feature of our patient 1 was the development of diabetes mellitus at the very early age of 2 months. There are only two patient reports of overt diabetes mellitus described at ages 4 and 5 months (12,18). Our patient is the youngest reported CGL patient with diabetes mellitus so far.…”

Section: Discussionmentioning

confidence: 99%

“…Hypertrophic cardiomyopathy is reported in 20–25% of CGL patients and is a significant cause of morbidity from cardiac failure and of early mortality (9,10,11,12). However, this life-threatening complication is usually reported in older patients.…”

Section: Discussionmentioning

confidence: 99%

“…Bhayana et al (11) described a young girl with CGL harboring a mutation in BSCL2, who was found to have myocardial hypertrophy from 6 months of age. In a 4-month-old Chinese boy, Friguls et al (12) reported severe cardiomyopathy with cardiac failure and systemic hypertension. Debray et al (14) reported a young boy presenting at age 1 month with severe hypertrophic cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

“…Diabetes mellitus usually appears by the second decade or in adulthood (5,6,7,8). Additionally, hypertrophic cardiomyopathy is a classical late (second or third decade) complication (9,10) which has only been occasionally described in infancy or childhood (11,12,13,14). Currently, the disease is classified into four types according to clinical characteristics and type of mutations.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Mutational Features of Three Chinese Children with Congenital Generalized Lipodystrophy

Su¹,

Lin²,

Huang³

et al. 2017

Jcrpe

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Objective:To investigate the clinical and molecular features of congenital generalized lipodystrophy (CGL) in three Chinese patients with various typical manifestations.Methods:Data on clinical symptoms, results of laboratory analyses, and previous treatments in three Chinese patients were collected by a retrospective review of medical records. All coding regions and adjacent exon–intron junction regions of AGPAT2 and BSCL2 genes were amplified by polymerase chain reaction and sequenced.Results:Generalized lipodystrophy, acanthosis nigricans, muscular hypertrophy, severe hypertriglyceridemia, and hepatomegaly were features in all three patients. Patient 1 developed diabetes mellitus at the early age of 2 months and he was the youngest CGL patient reported with overt diabetes. Patient 2 was found to have cardiomyopathy when she was aged 6 months. All of the patients were found to have mutations in the BSCL2 gene, but none of these was a novel mutation. We did not find any AGPAT2 mutation in our patients.Conclusion:All of our patients exhibited characteristic features of CGL due to mutations in the BSCL2 gene.

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High incidence of BSCL2 intragenic recombinational mutation in Peruvian type 2 Berardinelli–Seip syndrome

Purizaca-Rosillo

Mori

Benites-Cóndor

et al. 2016

American J of Med Genetics Pt A

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Congenital generalized lipodystrophy (CGL) is a genetically heterogeneous group of disorders characterized by the absence of functional adipose tissue. We identified two pedigrees with CGL in the community of the Mestizo tribe in the northern region of Peru. Five cases, ranging from 15 months to 7 years of age, presented with generalized lipodystrophy, muscular prominence, mild intellectual disability, and a striking aged appearance. Sequencing of the BSCL2 gene, known to be mutated in type 2 CGL (CGL2; Berardinelli–Seip syndrome), revealed a homozygous deletion of exon 3 in all five patients examined, suggesting the presence of a founder mutation. This intragenic deletion appeared to be mediated by recombination between Alu sequences in introns 2 and 3. CGL2 in this population is likely underdiagnosed and undertreated because of its geographical, socio-economic, and cultural isolation.

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

Cited by 29 publications

References 15 publications

A Patient with Congenital Generalized Lipodystrophy Due To a Novel Mutation in BSCL2: Indications for Secondary Mitochondrial Dysfunction

A Patient with Congenital Generalized Lipodystrophy Due To a Novel Mutation in BSCL2: Indications for Secondary Mitochondrial Dysfunction

Clinical and Mutational Features of Three Chinese Children with Congenital Generalized Lipodystrophy

High incidence of BSCL2 intragenic recombinational mutation in Peruvian type 2 Berardinelli–Seip syndrome

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