Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.
 ...
PMID:Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. 1147 39

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.
 ...
PMID:A Taiwanese boy with congenital generalized lipodystrophy caused by homozygous Ile262fs mutation in the BSCL2 gene. 2112 15

Congenital generalized lipodystrophies (CGLs) are a heterogeneous group of rare, monogenic disorders characterized by loss of sub-cutaneous fat, muscular hypertrophy, acanthosis nigricans, hepatomegaly, cardiac arrhythmias, impaired metabolism and mental retardation. Four different but overlapping phenotypes (CGL1-4) have been identified, which are caused by mutations in AGPAT2 at 9q34.3, BSCL2 at 11q13, CAV1 at 7q31.1, and PTRF at 17q21.2. In this study, we performed genome-wide homozygosity mapping of two affected and one unaffected subject in a Saudi family using a 300K HumanCytoSNPs12v12.1 array with the Illumina iScan system. A common homozygous region at chromosome 17q22.1, from 34.4 to 45.3 Mb, was identified in both the affected individuals. The region is flanked by SNPs rs139433362 and rs185263326, which encompass the PTRF gene. Bidirectional DNA sequencing of the PTRF gene covering all of the coding exons and exon-intron boundaries was performed in all family members. Sequencing analysis identified a novel homozygous nonsense mutation in the PTRF gene (c.550G>T; p.Glu184*), leading to a premature stop codon. To the best of our knowledge, we present a novel mutation of PTRF from Saudi Arabia and our findings broaden the mutation spectrum of PTRF in the familial CGL4 phenotype. Homozygosity mapping coupled with candidate gene sequencing is an effective tool for identifying the causative pathogenic variants in familial cases.
 ...
PMID:Novel nonsense mutation in the PTRF gene underlies congenital generalized lipodystrophy in a consanguineous Saudi family. 2572 73

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder with two major subtypes. Variants in AGPAT2 result in CGL type 1 with milder manifestations, whereas BSCL2 variants cause CGL type 2 with more severe features. Muscle hypertrophy caused by lack of adipose tissue is present early in life in CGL patients. Our aim was to investigate 10 CGL patients from 7 different countries and report genotype-phenotype relationships. Genetic analysis identified disease-causing variants in AGPAT2 (five patients) and in BSCL2 (five patients), including three novel variants; c.134C>A (p.Ser45*), c.216C>G (p.Tyr72*) in AGPAT2 and c.458C>A (p.Ser153*) in BSCL2. We also report possible novel clinical features such as anemia, breast enlargement, steatorrhea, intraventricular hemorrhage and nephrolithiasis in CGL patients. Generalized lipodystrophy and muscular hypertrophy were the only features in all of our patients. Hepatomegaly was the second common feature. Some manifestations were exclusively noticed in our CGL2 patients; hypertrichosis, high-pitched voice and umbilical hernia. Bone cysts and history of seizures were noticed only in CGL1 patients. The findings of this study expand our knowledge of genotype-phenotype correlations in CGL patients. These results have important clinical applications in diagnosis and management of the CGL patients as well as in genetic counseling in families at-risk.
 ...
PMID:Congenital generalized lipodystrophy: identification of novel variants and expansion of clinical spectrum. 2607 26

Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by lipoatrophy affecting the face, limbs and trunk, acromegaloid features, hepatomegaly, hypertriglyceridemia, and insulin resistance. The aim of this study is to evaluate the long-term follow-up findings including gastrointestinal and cardiac manifestations of the patients with CGL1 and CGL4, caused by mutations in the AGPAT2 and CAVIN1 genes, respectively. Two patients aged 2 and 9 years with the same biallelic CAVIN1 mutation and five patients aged between 6 months and 11 years 4 months with AGPAT2 mutations have been followed up for 3-9 years. The patients were between 7 and 20 years of age at their last examination. One of the two patients with CGL4 had congenital pyloric stenosis. The other patient with CGL4 have developed recurrent duodenal perforations which have not been reported in CGL patients previously. The pathological examination of duodenal specimens revealed increased subserosal fibrous tissue and absent submucosal adipose tissue. None of the five CGL1 patients had gastrointestinal problems. Two patients with CGL4 developed hypertrophic cardiomyopathy (HCMP) and severe cardiac arrhythmia, only one patient with CGL1 had HCMP. Hyperinsulinemia was detected in one patient with CGL4 and three patients with CGL1, these three CGL1 patients also had acanthosis nigricans. Hepatic steatosis was detected in one patient with CGL4 and two patients with CGL1 by ultrasonography. In conclusion, these findings suggest that CGL4 patients should also be carefully followed up for gastrointestinal and cardiac manifestations.
 ...
PMID:Congenital generalized lipodystrophy: The evaluation of clinical follow-up findings in a series of five patients with type 1 and two patients with type 4. 3177 56