LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090).
Hutchinson-Gilford progeria syndrome (HGPS; MIM 176670) is an extremely rare disease that is characterized by accelerated aging and early death, frequently from coronary artery disease. Wiedemann-Rautenstrauch syndrome (WRS; MIM 264090) is another extremely rare disease that is characterized by progeroid features from birth with multiple somatic anomalies and paucity of subcutaneous fat. Because mutations in LMNA, encoding nuclear lamin A/C, cause other lipodystrophy syndromes, we sequenced LMNA (MIM 150330) from the genomic DNAs of seven unrelated HGPS probands and two unrelated WRS probands. We found four novel LMNA coding sequence variants among the HGPS probands, namely R471C, R527C, G608S and c.2036C>T. All seven HGPS probands had at least one LMNA variant, which were found in none of the genomes of 100 normal subjects ( P<4 x 10(-11)). In contrast, neither of the WRS proband genomes had any LMNA sequence abnormality. The strong association of rare LMNA coding sequence mutations with HGPS implicates this syndrome as a laminopathy, while WRS is most probably due to mutations in another gene.
Cao
Henian
H
Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 406-100 Perth Drive, London, Ontario, N6A 5K8, Canada.
Hegele
Robert A
RA
Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, 406-100 Perth Drive, London, Ontario, N6A 5K8, Canada. hegele@robarts.ca.
D000293:Adolescent; D000328:Adult; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D009154:Mutation; D011371:Progeria / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
D034904:Lamin Type A; C440308:lamin C