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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：神经纤维瘤病1（NF1;OMIM＃162200）是一种常见的常染色体显性遗传病[发病率：〜1：3500]。在95%的案例中，该疾病的临床诊断基于7项美国国立卫生研究院诊断标准中的至少两项。这种疾病的分子病理学需要NF1基因的突变。这项研究的目的是调查埃及NF1患者队列的临床和分子特征。
方法：本研究包括35名临床诊断为NF1的患者，这些患者来自25个无关的家庭。患者的NIH诊断标准≥2。通过对多个重叠片段的直接cDNA测序来进行NF1基因的检查。这通过白细胞DNA的NF1多重连接依赖性探针扩增(MLPA)分析来补充。
结果：临床表现包括，100%的先证者中的咖啡点，雀斑(52%)，神经纤维瘤（20%），虹膜的Lisch结节（12％），视路胶质瘤（8%），典型的骨骼疾病（20％），家族史阳性（32%）。可在24个家族(96%)中检测到突变。八个突变（33％）是新的。
结论：这项研究首次说明了埃及NF1患者的潜在分子病理学。它还报道了NF1基因中8个新的突变，扩展了致病性突变谱。
方法：本研究包括35名临床诊断为NF1的患者，这些患者来自25个无关的家庭。患者的NIH诊断标准≥2。通过对多个重叠片段的直接cDNA测序来进行NF1基因的检查。这通过白细胞DNA的NF1多重连接依赖性探针扩增(MLPA)分析来补充。
结果：临床表现包括，100%的先证者中的咖啡点，雀斑(52%)，神经纤维瘤（20%），虹膜的Lisch结节（12％），视路胶质瘤（8%），典型的骨骼疾病（20％），家族史阳性（32%）。可在24个家族(96%)中检测到突变。八个突变（33％）是新的。
结论：这项研究首次说明了埃及NF1患者的潜在分子病理学。它还报道了NF1基因中8个新的突变，扩展了致病性突变谱。
