Medical Molecular Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Mol Genet Genomic Med. 2021 Dec;9(12):e1631. doi: 10.1002/mgg3.1631. Epub 2021 Jun 3.
Neurofibromatosis 1 (NF1; OMIM# 162200) is a common autosomal dominant genetic disease [incidence: ~1:3500]. In 95% of cases, clinical diagnosis of the disease is based on the presence of at least two of the seven National Institute of Health diagnostic criteria. The molecular pathology underlying this disorder entails mutation in the NF1 gene. The aim of this study was to investigate clinical and molecular characteristics of a cohort of Egyptian NF1 patients.
This study included 35 clinically diagnosed NF1 patients descending from 25 unrelated families. Patients had ≥2 NIH diagnostic criteria. Examination of NF1 gene was done through direct cDNA sequencing of multiple overlapping fragments. This was supplemented by NF1 multiple ligation dependent probe amplification (MLPA) analysis of leucocytic DNA.
The clinical presentations encompassed, café-au-lait spots in 100% of probands, freckling (52%), neurofibromas (20%), Lisch nodules of the iris (12%), optic pathway glioma (8%), typical skeletal disorders (20%), and positive family history (32%). Mutations could be detected in 24 families (96%). Eight mutations (33%) were novel.
This study illustrates the underlying molecular pathology among Egyptian NF1 patients for the first time. It also reports on 8 novel mutation expanding pathogenic mutational spectra in the NF1 gene.
神经纤维瘤病 1 型（NF1；OMIM#162200）是一种常见的常染色体显性遗传疾病[发病率：~1:3500]。在 95%的病例中，疾病的临床诊断基于至少存在 NIH 诊断标准的七个标准中的两个。该疾病的分子病理学涉及 NF1 基因的突变。本研究旨在研究一组埃及 NF1 患者的临床和分子特征。
本研究纳入了 35 名来自 25 个无关家族的临床诊断为 NF1 的患者。患者有≥2 个 NIH 诊断标准。通过对多个重叠片段的直接 cDNA 测序对 NF1 基因进行检查。这通过白细胞 DNA 的 NF1 多重连接依赖性探针扩增（MLPA）分析进行补充。
临床表型包括 100%的先证者有牛奶咖啡斑，52%有雀斑，20%有神经纤维瘤，12%有虹膜神经纤维瘤，8%有视路胶质瘤，20%有典型骨骼异常，32%有阳性家族史。可在 24 个家庭（96%）中检测到突变。8 个突变（33%）是新的。
本研究首次阐明了埃及 NF1 患者的潜在分子病理学，并报告了 8 个新的突变，扩展了 NF1 基因的致病性突变谱。
