Analysis of the NF1 gene by temperature gradient gel electrophoresis reveals a high incidence of mutations in exon 4b

被引：0

作者：

Toliat, Mohammed R. ^{[1
]}

Erdogan, Fikret ^{[1
]}

Gewies, Andreas ^{[1
]}

Fahsold, Raimund ^{[2
]}

Buske, Annegret ^{[1
]}

Tinschert, Sigrid ^{[1
]}

Nürnberg, Peter ^{[1
,3
]}

机构：

[1] Inst. für Medizinische Genetik, Universitatsklinikum Charite, Berlin, Germany

[2] Gemeinschaftspraxis B., Prager and A. Junge, Dresden, Germany

[3] Inst. für Medizinische Genetik, Universitatsklinikum Charite, D-10098 Berlin, Germany

来源：

| 2000年 / Wiley-VCH Verlag卷 / 21期

关键词：

Electrophoresis - Polymerase chain reaction - Thermal gradients;

D O I：

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摘要：

A total of 196 unrelated patients with neurofibromatosis type 1 (NF1) was screened for mutations in exons 4a-c of the NF1 gene by temperature gradient gel electrophoresis (TGGE) of polymerase chain reaction (PCR)- amplified genomic DNA fragments using intron-based primers. DNA samples with abnormal TGGE band patterns were subjected to sequence analysis. Sequence alterations were identified in ten patients (5.1%): 496delGT (1), 499delTGTT (4), T528A=D176E (2), T539A=L180X (1), 540insA (1), C574T=R192X (1). Thus, a total of six different mutations was identified in exon 4b but none in exons 4a and 4c. Only the missense mutation D176E, which we assume to be a nonpathogenic polymorphism, and the 4-base pair (bp) deletion 499delTGTT have been described before. The reason for the high incidence of mutations in exon 4b is obviously a tetranucleotide tandem repeat comprising nucleotides 495- 502 (TGTTTGTT) that may give rise to slipped mispairing and subsequent deletion of one repeat unit during replication. Additionally, the recurrent 4 bp deletion was found as a second hit in a malignant schwannoma of a further NF1 patient, suggesting that microlesions may be as frequent among somatic as among germline mutations. This is the first report of a systematic study of NF1 exons 4a-c in a large group of NF1 patients.

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