• autosomal recessive;
  • COFS syndrome;
  • CSB protein;
  • ERCC6 gene;
  • founder mutation

Jaakkola E, Mustonen A, Olsen P, Miettinen S, Savuoja T, Raams A, Jaspers NGJ, Shao H, Wu BL, Ignatius J. ERCC6 founder mutation identified in Finnish patients with COFS syndrome.

Cerebro-oculo-facio-skeletal (COFS) syndrome is an autosomal recessive disorder characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. We report a large consanguineous pedigree from northern Finland with six individuals belonging into four different sibships and affected with typical COFS syndrome phenotype. Two deceased patients have been published previously in 1982 as the first cases exhibiting cerebral calcifications typical for this disorder. Two living and one of the deceased patients were all shown to possess a novel homozygous mutation in the ERCC6 [Cockayne syndrome B (CSB)] gene, thereby confirming the diagnosis on molecular genetic level even for the earlier published cases. Genealogical investigation showed a common ancestor living in a northeastern village in Finland in the 18th century for all six patients implying a founder effect.