Open AccessThe effect of parental age on the presence of de novo mutations – Lessons from neurofibromatosis type I
Author(s) -
Dubov Tom,
ToledanoAlhadef Hagit,
Bokstein Felix,
Constantini Shlomi,
BenShachar Shay
Publication year - 2016
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.222
Subject(s) - medicine , neurofibromatosis , paternal age , family history , pediatrics , population , disease , demography , medical genetics , age of onset , genetics , pathology , biology , pregnancy , offspring , gene , environmental health , sociology
Background Neurofibromatosis type 1 ( NF 1) 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 NF 1 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 NF 1 pediatric patients followed in a specialized Israeli NF 1 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 NF 1 (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 NF 1 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. Conclusion Parents of sporadic NF 1 cases are older. The risk for sporadic NF 1 was lower when the fathers were younger at the time of the affected child's birth, and gradually increased with paternal age.