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Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli–Seip congenital generalized lipodystrophy syndrome
Author(s) -
Miranda Debora M.,
Wajchenberg Bernardo L.,
Calsolari Maria R.,
Aguiar Marcos J.,
Silva José M. C. L.,
Ribeiro Marcia G.,
Fonseca Cristina,
Amaral Daniela,
Boson Wolfanga L.,
Resende Bruna A.,
De Marco Luiz
Publication year - 2009
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2009.03532.x
Subject(s) - lipodystrophy , medicine , acanthosis nigricans , endocrinology , biology , genetics , mutation , gene , insulin resistance , insulin , virus , viral load , antiretroviral therapy
Summary Context 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. Design 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).