title: Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli-Seip congenital generalized lipodystrophy syndrome.
abstract: BACKGROUND
  Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome, is a rare autosomal recessive disease caused by mutations in either the BSCL2 or AGPAT2 genes. This syndrome is characterized by an almost complete loss of adipose tissue usually diagnosed at birth or early infancy resulting in apparent muscle hypertrophy. Common clinical features are acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present.
  
  
  METHODS
  We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly.
  
  
  RESULTS
  Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C>T c.464T>C, c.518-519insA, IVS5-2A>G), and in two kindreds compound mutations were found (c.1363C>T, c.424A>G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3-1G>C and c.299G>A).
  
  
  CONCLUSIONS
  We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli-Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome).
authors.affiliation: Department of Paediatrics, Universidade Federal de Minas Gerais, Avenue Antonio Carlos 6627, Belo Horizonte, Brazil.
authors.forename: Debora M
authors.initials: DM
authors.lastname: Miranda
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Wajchenberg
authors.forename: Maria R
authors.initials: MR
authors.lastname: Calsolari
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Aguiar
authors.forename: José M C L
authors.initials: JM
authors.lastname: Silva
authors.forename: Marcia G
authors.initials: MG
authors.lastname: Ribeiro
authors.forename: Cristina
authors.initials: C
authors.lastname: Fonseca
authors.forename: Daniela
authors.initials: D
authors.lastname: Amaral
authors.forename: Wolfanga L
authors.initials: WL
authors.lastname: Boson
authors.forename: Bruna A
authors.initials: BA
authors.lastname: Resende
authors.forename: Luiz
authors.initials: L
authors.lastname: De Marco
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001938:Brazil; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D006801:Humans; D007223:Infant; D052497:Lipodystrophy, Congenital Generalized / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction
chemical_list: C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase