Dubov Tom, Toledano-Alhadef Hagit, Bokstein Felix, Constantini Shlomi, Ben-Shachar Shay
Sackler Faculty of Medicine Tel-Aviv University Tel-Aviv Israel.
Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael; The Gilbert Israeli Neurofibromatosis CenterTel-Aviv Medical CenterTel-AvivIsrael.
Mol Genet Genomic Med. 2016 Jun 16;4(4):480-6. doi: 10.1002/mgg3.222. eCollection 2016 Jul.
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.
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.
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.
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.
1型神经纤维瘤病（NF1）是最常见的常染色体显性神经皮肤疾病，患病率为1:2500。大约50%的病例为散发性。父亲年龄较大与生殖系突变和常染色体疾病有关。我们旨在以NF1为范例，研究父母年龄对散发性突变率的影响，包括父母年龄较大和较小时的情况。
对以色列一家专门的NF1诊所随访的118例NF1儿科患者的病历进行评估。31例通过基因检测确诊，87例根据美国国立卫生研究院（NIH）临床标准确诊。64例（54%）患者有NF1阴性家族史（散发病例）。将孩子出生时父母的年龄数据与全国人口数据库进行比较。
散发性NF1患儿的父母年龄高于一般人群（母亲分别为32.7岁和30.1岁，父亲分别为36.5岁和32.6岁；两组P均<0.0001）。相比之下，家族性病例中母亲和父亲的年龄（分别为30.岁和33.9岁）与一般人群无差异。值得注意的是，与一般人群中的父亲相比，散发性组中孩子出生时年龄在25 - 29岁的父亲较少（分别为7.8%和21%，P = 0.009），而年龄≥40岁的父亲明显更多（分别为29.7%和13.6%，P = 0.0002）。两组母亲年龄的差异不太显著。
散发性NF1病例的父母年龄较大。当受影响孩子出生时父亲年龄较小时，散发性NF1的风险较低，并随父亲年龄逐渐增加。
