Lipodystrophy, familial partial, type 6

Alternative name(s) : FPLD6, Lipodystrophy, familial partial, associated with LIPE mutations, LIPE-related lipodystrophic syndrome, LIPE-related Multiple Symmetric Lipomatosis (MSL), LIPE-related Launois-Bensaude Lipomatosis or Madelung disease

Gene_locus : human-LIPE

Mutation : 3 mutations V767GfsX_human-LIPE A507fsX_human-LIPE E1035X_human-LIPE

OMIM : 615980 , 151750

Comment

(from OMIM) Albert et al. (2014) sequenced 12 lipolytic-pathway genes in 24 Old Order Amish individuals whose fasting serum triglyceride levels were at the extremes of the distribution, and detected a 19-bp deletion in the LIPE gene in an individual whose triglyceride level was at the upper extreme. Genotyping for the LIPE deletion in 2,738 participants in the Amish Complex Disease Research Program identified 1 individual who was homozygous for the deletion ('DD' genotype) and 140 heterozygotes. Homozygous individuals exhibited impaired lipolysis and showed evidence for redistribution of body fat as well as altered metabolic traits, including systemic insulin resistance and diabetes. Carriers of the deletion had an increased risk of metabolic dysfunction. In an Italian sister and brother from a consanguineous family with a late-onset form of partial lipodystrophy, originally reported by Carboni et al. (2014), Farhan et al. (2014) performed genomewide autozygosity mapping and whole-exome sequencing, and identified a frameshift mutation in the LIPE gene that segregated with disease in the family. Sollier et al. (2021) describe four novel mutations in three patients and model the disease using stem cells