Type A insulin resistance syndrome revealing a novel lamin A mutation.
Particular forms of polycystic ovary syndrome with severe hyperandrogenism, acanthosis nigricans, and marked insulin resistance, defining the type A insulin resistance syndrome, are due to insulin receptor gene mutations. However, the majority of affected individuals do not have such mutation, arguing for the genetic heterogeneity of this syndrome. The familial partial lipodystrophy of the Dunnigan type, one of the diseases due to mutations in the lamin A/C (LMNA) gene, is characterized by a lipodystrophic phenotype and shares some clinical and metabolic features with the type A syndrome. We describe here the case of a nonobese 24-year-old woman affected with type A syndrome without clinical lipodystrophy. We linked this phenotype to a novel heterozygous missense mutation in the LMNA, predicting a G602S amino acid substitution in lamin A. This mutation cosegregated with impaired glucose tolerance, insulin resistance, and acanthosis nigricans in the absence of clinical lipodystrophy in the family. The skin fibroblasts from the proband exhibited nuclear alterations similar to those described in other laminopathies, and showed several defects in the insulin transduction pathway. This study further extends the vast range of diseases linked to LMNA mutations and identifies another genetic cause for the type A insulin resistance syndrome.
Young
Jacques
J
Saint-Antoine Faculty of Medicine, INSERM U680, 27 rue Chaligny, 75 571 Paris Cedex 12, France.
Morbois-Trabut
Louise
L
Couzinet
Béatrice
B
Lascols
Olivier
O
Dion
Elisabeth
E
Béréziat
Véronique
V
Fève
Bruno
B
Richard
Isabelle
I
Capeau
Jacqueline
J
Chanson
Philippe
P
Vigouroux
Corinne
C
D000328:Adult; D005260:Female; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics*; D034904:Lamin Type A / Q000235:genetics*; D009154:Mutation; D009839:Oligomenorrhea / Q000235:genetics; D013577:Syndrome
D034904:Lamin Type A