TY - JOUR T1 - Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy JF - Journal of Medical Genetics JO - J Med Genet SP - 722 LP - 733 DO - 10.1136/jmg.39.10.722 VL - 39 IS - 10 AU - L Van Maldergem AU - J Magré AU - T E Khallouf AU - T Gedde-Dahl, Jr AU - M Delépine AU - O Trygstad AU - E Seemanova AU - T Stephenson AU - C S Albott AU - F Bonnici AU - V R Panz AU - J-L Medina AU - P Bogalho AU - F Huet AU - S Savasta AU - A Verloes AU - J-J Robert AU - H Loret AU - M de Kerdanet AU - N Tubiana-Rufi AU - A Mégarbané AU - J Maassen AU - M Polak AU - D Lacombe AU - C R Kahn AU - E L Silveira AU - F H D’Abronzo AU - F Grigorescu AU - M Lathrop AU - J Capeau AU - S O’Rahilly Y1 - 2002/10/01 UR - http://jmg.bmj.com/content/39/10/722.abstract N2 - 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. ER -