Dataset Information

Clinical characteristics and mutation Spectrum of NF1 in 12 Chinese families with orbital/periorbital plexiform Neurofibromatosis type 1.

ABSTRACT:

Background

Orbital/periorbital plexiform neurofibroma (OPPN) can compromise physical appearance and visual function. However, the clinical characteristics and NF1 mutation landscape in patients with heritable OPPN have not been reported.

Methods

The medical charts of 26 Chinese patients with OPPN from 12 families were reviewed. Mutation analysis of the entire coding region and flanking splice sites of the NF1 gene was performed using next-generation sequencing (NGS). Novel NF1 mutations were confirmed by Sanger sequencing.

Results

Compared to the parental generation, a significantly larger proportion of OPPN patients in the successive generation presented with earlier onset (p?=?0.001), amblyopia (p?=?0.034), motility disorders (p?=?0.009) and bony orbital expansion (p?=?0.019). Six novel NF1 mutations were identified in 11 (91.67%) families, including 6 (42.9%) single-base substitutions, 4 (28.5%) splicing mutations, 3 (21.4%) frameshift deletions, and 1 (7.14%) intron mutation.

Conclusions

The successive generation of OPPN patients presented with earlier onset and exhibited more severe ocular signs than did their parents or grandparents. Special attention should be paid to successive generations of OPPN patients. Considering that 6 mutations were novel, comprehensive NF1 mutation analysis is required or necessary or proposed for genetic counselling.

SUBMITTER: Chai P

PROVIDER: S-EPMC6749707 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinical characteristics and mutation Spectrum of NF1 in 12 Chinese families with orbital/periorbital plexiform Neurofibromatosis type 1.

Chai Peiwei P Luo Yingxiu Y Zhou Chuandi C Wang Yefei Y Fan Xianqun X Fan Xianqun X Jia Renbing R

BMC medical genetics 20190918 1

<h4>Background</h4>Orbital/periorbital plexiform neurofibroma (OPPN) can compromise physical appearance and visual function. However, the clinical characteristics and NF1 mutation landscape in patients with heritable OPPN have not been reported.<h4>Methods</h4>The medical charts of 26 Chinese patients with OPPN from 12 families were reviewed. Mutation analysis of the entire coding region and flanking splice sites of the NF1 gene was performed using next-generation sequencing (NGS). Novel NF1 mut ...[more]

PMID: 31533651

Similar Datasets

Project description:Neurofibromatosis type 1 (NF1) is a common tumor-predisposition disorder due to germline mutations in the tumor suppressor gene NF1. A virtually pathognomonic finding of NF1 is the plexiform neurofibroma (PN), a benign, likely congenital tumor that arises from bi-allelic inactivation of NF1. PN can undergo transformation to a malignant peripheral nerve sheath tumor, an aggressive soft-tissue sarcoma. To better understand the non-NF1 genetic contributions to PN pathogenesis, we performed whole-exome sequencing, RNASeq profiling and genome-wide copy-number determination for 23 low-passage Schwann cell cultures established from surgical PN material with matching germline DNA. All resected tumors were derived from routine debulking surgeries. None of the tumors were considered at risk for malignant transformation at the time; for example, there was no pain or rapid growth. Deep (~500X) NF1 exon sequencing was also conducted on tumor DNA. Non-NF1 somatic mutation verification was performed using the Ampliseq/IonTorrent platform. We identified 100% of the germline NF1 mutations and found somatic NF1 inactivation in 74% of the PN. One individual with three PNs had different NF1 somatic mutations in each tumor. The median number of somatic mutations per sample, including NF1, was one (range 0-8). NF1 was the only gene that was recurrently somatically inactivated in multiple tumors. Gene Set Enrichment Analysis of transcriptome-wide tumor RNA sequencing identified five significant (FDR<0.01) and seven trending (0.01⩽FDR<0.02) gene sets related to DNA replication, telomere maintenance and elongation, cell cycle progression, signal transduction and cell proliferation. We found no recurrent non-NF1 locus copy-number variation in PN. This is the first multi-sample whole-exome and whole-transcriptome sequencing study of NF1-associated PN. Taken together with concurrent copy-number data, our comprehensive genetic analysis reveals the primacy of NF1 loss as the driver of PN tumorigenesis.

Dataset Information

Clinical characteristics and mutation Spectrum of NF1 in 12 Chinese families with orbital/periorbital plexiform Neurofibromatosis type 1.

Background

Methods

Results

Conclusions

Publications

Clinical characteristics and mutation Spectrum of NF1 in 12 Chinese families with orbital/periorbital plexiform Neurofibromatosis type 1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets