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Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13
- Source :
- Nature genetics. 28(4)
- Publication Year :
- 2001
-
Abstract
- Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.
- Subjects :
- Genetic Markers
Male
medicine.medical_specialty
Lipodystrophy
Genetic Linkage
BSCL2
DNA Mutational Analysis
Molecular Sequence Data
Locus (genetics)
Genes, Recessive
Biology
Acquired generalized lipodystrophy
Seipin
Congenital generalized lipodystrophy
Diabetes Complications
Genetic linkage
Internal medicine
GTP-Binding Protein gamma Subunits
Genetics
medicine
Cluster Analysis
Humans
Acanthosis Nigricans
Genetic Testing
Lebanon
Hypertriglyceridemia
Sequence Homology, Amino Acid
Norway
Chromosomes, Human, Pair 11
Proteins
Middle Aged
medicine.disease
Familial partial lipodystrophy
Heterotrimeric GTP-Binding Proteins
Pedigree
Protein Structure, Tertiary
Endocrinology
Haplotypes
Organ Specificity
Mutation
Female
Insulin Resistance
Chromosomes, Human, Pair 9
Hyperandrogenism
Hepatomegaly
Subjects
Details
- ISSN :
- 10614036
- Volume :
- 28
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Nature genetics
- Accession number :
- edsair.doi.dedup.....33f1d317e44baa847de028fb9ade2222