Two Japanese infants with congenital generalized lipodystrophy due to <i>BSCL2</i> mutations

Nishiyama, Atsushi; Yagi, Minoru; Awano, Hiroyuki; Okizuka, Yo; Maeda, Taro; Yoshida, Shinsaku; Takeshima, Yasuhiro; Matsuo, Masafumi

doi:10.1111/j.1442-200x.2009.02863.x

Cited by 11 publications

(6 citation statements)

References 31 publications

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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].…”

Section: Discussionsupporting

confidence: 61%

Deletion mutation in BSCL2 gene underlies congenital generalized lipodystrophy in a Pakistani family

et al. 2013

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BackgroundCongenital 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.MethodsThe 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.ResultsSequence 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.ConclusionMutation 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 SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1913913076864247.

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Section: Discussionsupporting

confidence: 61%

Deletion mutation in BSCL2 gene underlies congenital generalized lipodystrophy in a Pakistani family

et al. 2013

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“…As described, mutations for CGL patients can be homozygous or compound heterozygous, and most of the BSCL2 mutations are nonsense or frameshift mutations that are expected to cause loss of function of the protein [9]. Reports from Japan, India, China and Taiwan [9,[13][14][15][16][17][18] indicate that BSCL2 is a major causative gene for CGL in Asian (Table). However, nearly 50% of CGL cases around the world have no sequence mutation in either AGPAT2 or BSCL2 [19].…”

Section: Discussionmentioning

confidence: 99%

A Taiwanese Boy With Congenital Generalized Lipodystrophy Caused by Homozygous Ile262fs Mutation in the BSCL2 Gene

Huang

Chen

Hsiao

et al. 2010

The Kaohsiung J of Med Scie

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Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disease that is characterized by a near-complete absence of adipose tissue from birth or early infancy. Mutations in the BSCL2 gene are known to result in CGL2, a more severe phenotype than CGL1, with earlier onset, more extensive fat loss and biochemical changes, more severe intellectual impairment, and more severe cardiomyopathy. We report a 3-month-old Taiwanese boy with initial presentation of a lack of subcutaneous fat, prominent musculature, generalized eruptive xanthomas, and extreme hypertriglyceridemia. Absence of mechanical adipose tissue in the orbits and scalp was revealed by head magnetic resonance imaging. Hepatomegaly was noticed, and histological examination of a liver biopsy specimen suggested severe hepatic steatosis and periportal necrosis. However, echocardiography indicated no sign of cardiomyopathy and he showed no distinct intellectual impairment that interfered with daily life. About 1 year later, abdominal computed tomography revealed enlargement of kidneys. He had a homozygous insertion of a nucleotide, 783insG (Ile262fs mutation), in exon 7 of the BSCL2 gene. We reviewed the genotype of CGL cases from Japan, India, China and Taiwan, and found that BSCL2 is a major causative gene for CGL in Asian.

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“…Congenital lipoatrophy is a rare autosomal recessive condition often associated with consanguineous marriage [179; 167]. Approximately 100 subjects have been studied in the context of small, uncontrolled interventional studies, which have shown that leptin replacement dramatically improves dyslipidemia and insulin sensitivity in these individuals and reduces glycosylated hemoglobin, hepatic gluconeogenesis, and hepatic fat content [173; 182; 108; 109].…”

Section: Emerging Clinical Applicationsmentioning

confidence: 99%

Leptin in human physiology and therapeutics

Dardeno

Chou

Moon

et al. 2010

Frontiers in Neuroendocrinology

247

198

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Leptin regulates energy homeostasis and reproductive, neuroendocrine, immune, and metabolic functions. In this review, we describe the role of leptin in human physiology and review evidence from recent “proof of concept” clinical trials using recombinant human leptin in subjects with congenital leptin deficiency, hypoleptinemia associated with energy-deficient states, and hyperleptinemia associated with garden-variety obesity. Since most obese individuals are largely leptin-tolerant or -resistant, therapeutic uses of leptin are currently limited to patients with complete or partial leptin deficiency, including hypothalamic amenorrhea and lipoatrophy. Leptin administration in these energy-deficient states may help restore associated neuroendocrine, metabolic, and immune function and bone metabolism. Leptin treatment is currently available for individuals with congenital leptin deficiency and congenital lipoatrophy. The long-term efficacy and safety of leptin treatment in hypothalamic amenorrhea and acquired lipoatrophy are currently under investigation. Whether combination therapy with leptin and potential leptin sensitizers will prove effective in the treatment of garden-variety obesity and whether leptin may have a role in weight loss maintenance is being greatly anticipated.

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Two Japanese infants with congenital generalized lipodystrophy due to BSCL2 mutations

Abstract: Japanese CGL patients with BSCL2 mutations presented with severe insulin resistance, even during infancy, prior to the development of diabetes mellitus.

Cited by 11 publications

References 31 publications

Deletion mutation in BSCL2 gene underlies congenital generalized lipodystrophy in a Pakistani family

Deletion mutation in BSCL2 gene underlies congenital generalized lipodystrophy in a Pakistani family

A Taiwanese Boy With Congenital Generalized Lipodystrophy Caused by Homozygous Ile262fs Mutation in the BSCL2 Gene

Leptin in human physiology and therapeutics

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