Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy
| Autor: | P. Bogalho, O. Trygstad, Frédéric Huet, F. Bonnici, J.-J. Robert, Jacqueline Capeau, Tobias Gedde-Dahl, Didier Lacombe, E. Seemanova, T. E. Khallouf, André Mégarbané, Florin Grigorescu, J. L. Medina, Estevan Luiz da Silveira, Michel Polak, Vanessa R. Panz, C. S. Albott, Marc Delepine, L. Van Maldergem, H. Loret, Stephen O'Rahilly, M. De Kerdanet, Johannes A Maassen, Mark Lathrop, C R Kahn, T. Stephenson, F. H. D'abronzo, J. Magre, N. Tubiana-Rufi, S. Savasta, Alain Verloes |
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| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Genotype Lipodystrophy Genetic counseling BSCL2 Physiology Hyperlipidemias Biology Seipin Cohort Studies Congenital generalized lipodystrophy GTP-Binding Protein gamma Subunits Internal medicine Genetics medicine Humans Protein Isoforms Age of Onset Alleles Genetics (clinical) Generalized lipodystrophy Infant Newborn Infant medicine.disease Heterotrimeric GTP-Binding Proteins Pedigree Phenotype Endocrinology Mutation Original Article Female Age of onset |
| Zdroj: | Scopus-Elsevier |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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