Novel mutations of the <i>BSCL2</i> and <i>AGPAT2</i> genes in 10 families with Berardinelli–Seip congenital generalized lipodystrophy syndrome

Miranda, Débora Marques de; Wajchenberg, B. L.; Calsolari, Maria Regina; Aguiar, Marcos José Burle de; Silva, José M. C. L.; Ribeiro, Márcia Gonçalves; Fonseca, Cristina; Amaral, Daniela Patti do; Boson, Wolfanga L.; Resende, Bruna Araújo Martins; Marco, Luiz

doi:10.1111/j.1365-2265.2009.03532.x

Cited by 36 publications

(38 citation statements)

References 17 publications

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“…Mutations in three different genes (AGPAT2, BSCL2, and CAV1) have been identified to cause CGL type III [Agarwal et al, 2004;Ebihara et al, 2004;Miranda et al, 2009]. Mutations in PTRF-CAVIN were identified in CGL type IV [Cohn et al, 2007].…”

Section: Introductionmentioning

confidence: 98%

Marfan syndrome with neonatal progeroid syndrome‐like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1‐gene

Graul‐Neumann

Kienitz

Robinson

et al. 2010

American J of Med Genetics Pt A

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We report on a 25-year-old woman with pronounced generalized lipodystrophy and a progeroid aspect since birth, who also had Marfan syndrome (MFS; fulfilling the Ghent criteria) with mild skeletal features, dilated aortic bulb, dural ectasia, bilateral subluxation of the lens, and severe myopia in addition to the severe generalized lipodystrophy. She lacked insulin resistance, hypertriglyceridemia, hepatic steatosis, and diabetes. Mutation analysis in the gene encoding fibrillin 1 (FBN1) revealed a novel de novo heterozygous deletion, c.8155_8156del2 in exon 64. The severe generalized lipodystrophy in this patient with progeroid features has not previously been described in other patients with MFS and FBN1 mutations. We did not find a mutation in genes known to be associated with congenital lipodystrophy (APGAT2, BSCL2, CAV1, PTRF-CAVIN, PPARG, LMNB2) or with Hutchinson-Gilford progeria (ZMPSTE24, LMNA/C). Other progeria syndromes were considered unlikely because premature greying, hypogonadism, and scleroderma-like skin disease were not present. Our patient shows striking similarity to two patients who have been published in this journal by O'Neill et al. [O'Neill et al. (2007); Am J Med Genet Part A 143A:1421-1430] with the diagnosis of neonatal progeroid syndrome (NPS). This condition also known as Wiedemann-Rautenstrauch syndrome is a rare disorder characterized by accelerated aging and lipodystrophy from birth, poor postnatal weight gain, and characteristic facial features. The course is usually progressive with early lethality. However this entity seems heterogeneous. We suggest that our patient and the two similar cases described before represent a new entity, a subgroup of MFS with overlapping features to NPS syndrome.

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Section: Introductionmentioning

confidence: 98%

Marfan syndrome with neonatal progeroid syndrome‐like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1‐gene

Graul‐Neumann

Kienitz

Robinson

et al. 2010

American J of Med Genetics Pt A

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“…The primary transcript originally described ( 16 ) contained 11 exons with protein coding beginning (see below). Two additional missense mutations that cause lipodystrophy, not seipinopathy, are also located close to this glycosylation site; these are T78A and L91P ( 46 ). The L91 residue is particularly interesting in that it is well conserved among species that contain the NVS glycosylation site ( 45 ), indicating that this region of the protein may be critical for both protein stability and seipin function.…”

Section: Seipin Structurementioning

confidence: 99%

“…Magre et al ( 16 ) initially reported three main seipin mRNA isoforms in humans by Northern blotting at ‫ف‬ 1.8, ‫ف‬ 2.0, and ‫ف‬ 2.4 kb, considered in subsequent studies (and mutation, T78A (described below), in their other allele ( 46 ). It is surprising that this 7 amino acid deletion could generate lipodystrophy, since the C-terminal cytosolic tail is not required for fat body lipid accumulation in fl ies (see below) ( 47 ).…”

Section: Humansmentioning

confidence: 99%

Seipin: from human disease to molecular mechanism

Cartwright

Goodman²

2012

Journal of Lipid Research

115

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“…Several dozen disease-causing variants have been described. 2 The following molecular defects have been reported: nonsense, missense, splice-site variants, deletions and insertions. 3 Most of them result in frameshift and/or truncated proteins, which are likely to lead to the complete loss of AGPAT2 function.…”

Section: Mutational Spectrummentioning

confidence: 99%

Clinical Utility Gene Card for: Congenital Generalized Lipodystrophy

et al. 2016

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Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli–Seip congenital generalized lipodystrophy syndrome

Abstract: We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli-Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome).

Cited by 36 publications

References 17 publications

Marfan syndrome with neonatal progeroid syndrome‐like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1‐gene

Marfan syndrome with neonatal progeroid syndrome‐like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1‐gene

Seipin: from human disease to molecular mechanism

Clinical Utility Gene Card for: Congenital Generalized Lipodystrophy

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