title: The effect of parental age on the presence of de novo mutations - Lessons from neurofibromatosis type I.
abstract: BACKGROUND
  Neurofibromatosis type 1 (NF1) is the most common autosomal dominant neurocutaneous disease with a prevalence of 1:2500. Approximately, 50% of the cases are sporadic. Advanced paternal age is associated with germline mutations and autosomal diseases. We aimed to use NF1 as a paradigm to study the effect of parental age on sporadic mutation rates for both advanced and younger parental ages.
  
  
  METHODS
  The medical charts of 118 NF1 pediatric patients followed in a specialized Israeli NF1 clinic were evaluated. Thirty-one cases were diagnosed by genetic tests and 87 by NIH clinical criteria. Sixty-four cases (54%) had a negative family history of NF1 (sporadic cases). Data on parental ages at the time of the children's birth were compared to the national population database.
  
  
  RESULTS
  Parental age of children with sporadic NF1 was higher than the general population (32.7 years vs. 30.1 years, respectively, for the mothers and 36.5 years vs. 32.6 years, respectively, for the fathers; P < 0.0001 for both groups). In contrast, the age of the mothers and the fathers in the familial cases (30.3 and 33.9 years, respectively) did not differ from the general population. Significantly, fewer fathers of the sporadic group had been 25-29 years old at their child's birth compared with fathers in the general population (7.8% vs. 21%, respectively, P = 0.009), and significantly more fathers were ≥40 years old (29.7% vs. 13.6%, respectively, P = 0.0002). Differences in maternal age between these two groups were less prominent.
  
  
  CONCLUSIONS
  Parents of sporadic NF1 cases are older. The risk for sporadic NF1 was lower when the fathers were younger at the time of the affected child's birth, and gradually increased with paternal age.
authors.affiliation: Sackler Faculty of Medicine Tel-Aviv University Tel-Aviv Israel.
authors.forename: Tom
authors.initials: T
authors.lastname: Dubov
authors.affiliation: Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael; The Gilbert Israeli Neurofibromatosis CenterTel-Aviv Medical CenterTel-AvivIsrael.
authors.forename: Hagit
authors.initials: H
authors.lastname: Toledano-Alhadef
authors.affiliation: Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael; The Gilbert Israeli Neurofibromatosis CenterTel-Aviv Medical CenterTel-AvivIsrael.
authors.forename: Felix
authors.initials: F
authors.lastname: Bokstein
authors.affiliation: Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael; The Gilbert Israeli Neurofibromatosis CenterTel-Aviv Medical CenterTel-AvivIsrael; Department of Pediatric NeurosurgeryDana Children's Hospital, Tel-Aviv Medical CenterTel-AvivIsrael.
authors.forename: Shlomi
authors.initials: S
authors.lastname: Constantini
authors.affiliation: Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael; The Gilbert Israeli Neurofibromatosis CenterTel-Aviv Medical CenterTel-AvivIsrael.
authors.forename: Shay
authors.initials: S
authors.lastname: Ben-Shachar
keywords: Advanced paternal age; autosomal dominant; de novo; sporadic neurofibromatosis type 1