RT Journal Article
SR Electronic
T1 Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 722
OP 733
DO 10.1136/jmg.39.10.722
VO 39
IS 10
A1 L Van Maldergem
A1 J Magré
A1 T E Khallouf
A1 T Gedde-Dahl, Jr
A1 M Delépine
A1 O Trygstad
A1 E Seemanova
A1 T Stephenson
A1 C S Albott
A1 F Bonnici
A1 V R Panz
A1 J-L Medina
A1 P Bogalho
A1 F Huet
A1 S Savasta
A1 A Verloes
A1 J-J Robert
A1 H Loret
A1 M de Kerdanet
A1 N Tubiana-Rufi
A1 A Mégarbané
A1 J Maassen
A1 M Polak
A1 D Lacombe
A1 C R Kahn
A1 E L Silveira
A1 F H D’Abronzo
A1 F Grigorescu
A1 M Lathrop
A1 J Capeau
A1 S O’Rahilly
YR 2002
UL http://jmg.bmj.com/content/39/10/722.abstract
AB Generalised lipodystrophy of the Berardinelli-Seip type (BSCL) is a rare autosomal recessive human disorder with severe adverse metabolic consequences. A gene on chromosome 9 (BSCL1) has recently been identified, predominantly in African-American families. More recently, mutations in a previously undescribed gene of unknown function (BSCL2) on chromosome 11, termed seipin, have been found to be responsible for this disorder in a number of European and Middle Eastern families. We have studied the genotype/phenotype relationships in 70 affected subjects from 44 apparently unrelated pedigrees of diverse ethnic origin. In all subjects, hepatic dysfunction, hyperlipidaemia, diabetes mellitus, and hypertrophic cardiomyopathy were significant contributors to morbidity with no clear differences in their prevalence between subjects with BSCL1 or BSCL2 and those with evidence against cosegregation with either chromosome 9 or 11 (designated BSCLX). BSCL2 appears to be a more severe disorder than BSCL1 with a higher incidence of premature death and a lower prevalence of partial and/or delayed onset of lipodystrophy. Notably, subjects with BSCL2 had a significantly higher prevalence of intellectual impairment than those with BSCL1 or BSCLX (p<0.0001, OR 17.0, CI 3.6 to 79.0). The higher prevalence of intellectual impairment and the increased risk of premature death in BSCL2 compared to BSCL1 emphasise the importance of molecular diagnosis of this syndrome and have clear implications for genetic counselling.