A new Turkish family with homozygous FBXO7 truncating mutation and juvenile atypical parkinsonism

• DOI: 10.1016/j.parkreldis.2014.06.024
• Publication Date: 2014-07-22T01:15:39Z
• Authors: Gul Yalcin-Cakmakli; Simone Olgiati; Marialuisa Quadri; Guido J. Breedveld; Pietro Cortelli; Vincenzo Bonifati; Bulent Elibol
• Keywords: Male; 0301 basic medicine; Adolescent; Turkey; F-Box Proteins; Homozygote; Genes, Recessive; Pedigree; 3. Good health; Young Adult; 03 medical and health sciences; Parkinsonian Disorders; Mutation; Humans; Female; Genetic Predisposition to Disease; FBXO7; Gene; Juvenile; Mutation; Parkinsonism; Turkey; Adolescent; F-Box Proteins; Female; Genes, Recessive; Genetic Testing; Humans; Male; Mutation; Parkinsonian Disorders; Pedigree; Turkey; Young Adult; Genetic Predisposition to Disease; Homozygote; Genetic Testing

Juvenile parkinsonism can be caused by recessive mutations in several genes. Among these, homozygous or compound heterozygous mutations in the F-box only protein 7 gene (FBXO7) cause juvenile parkinsonism with variable degrees of pyramidal disturbances (PARK15). So far, only five families (from Iran, Italy, The Netherlands, Pakistan, and Turkey) have been reported with this form. Here, we describe a new Turkish family with homozygous FBXO7 mutation (c.1492C > T, p.Arg498*). Three out of nine siblings born from consanguineous parents suffered from juvenile-onset progressive parkinsonism. Mental retardation was also documented in two of them. Of note, pyramidal signs were absent. The response to dopaminergic medications was present, but limited by dyskinesias and psychiatric side effects. Further genetic analysis of this Turkish family and the Italian PARK15 family reported previously revealed that the c.1492C > T mutation is present on two different haplotypes in the Italian family, and one of these haplotypes is shared in homozygous state in the Turkish patients. These findings contribute to the ongoing delineation of the genetic and clinical spectrum of PARK15.