OBJECTIVE: To explore the molecular basis for a Chinese family affected with neurofibromatosis type I. METHODS: Peripheral blood samples were collected from the proband and his parents. Potential mutations of NF1 gene were screened by PCR and Sanger sequencing. Pathogenicity of candidate mutations was analyzed using Polyphen-2 and Provean software. RESULTS: Two mutations of the NF1 gene, including c.702G>A (synonymous mutation) and c.1733T>G (missense mutation), were discovered in the proband. Neither mutation was found in his parents and 50 healthy controls. Bioinformatics analysis indicated that the c.1733T>G mutation (p.Leu578Arg) was probably damaging. The affected codon L578 is highly conserved across various species. CONCLUSION The c.1733T>C mutation of the NF1 gene probably underlies the neurofibromatosis type I in this family.
Asian Continental Ancestry Group ; Genes, Neurofibromatosis 1 ; Humans ; Mutation ; Neurofibromatosis 1 ; genetics ; Neurofibromin 1 ; genetics ; Pedigree

OBJECTIVETo detect NF1 gene mutation in a patient with neurofibromatosis type 1.

METHODSFive fragments encompassing the entire coding sequence of the NF1 gene were amplified with reverse transcription PCR. PCR products were directly sequenced. Suspected mutations were verified by sequencing of DNA amplified by PCR using genomic DNA as template. Corresponding exon of family members was also sequenced. Furthermore, the PCR products were inserted into a pGEM-T cloning vector to quantify cells carrying the mutation in different samples derived from the three embryonic layers.

RESULTSThe proband's clinical manifestation was consistent with neurofibromatosis type 1. Sequence analysis has identified a novel heterozygous mutation c.7911 C to T (p.Q2510X) in exon 51 of the NF1 gene in the proband. The same mutation was also detected in peripheral blood cells, uroepithelial cells and oral mucosal cells of the proband, though the signals of uroepithelial cells were significantly weaker. By T cloning-sequencing, recombinants carrying the NF1 gene mutation respectively accounted for 42%, 36% and 12% of all peripheral blood cells, oral mucosal cells and uroepithelial cells .

CONCLUSIONIt is likely that a mutation of NF1 gene has occurred in early embryogenesis of the proband, which in turn has led to generalized mosaicism of neurofibromatosis type 1.

OBJECTIVE: To detect variants of NF1 gene among thirteen patients with neurofibromatosis type 1. METHODS: Genomic DNA was extracted from peripheral blood samples of the patients. High-throughput sequencing was employed to detect potential variants of the NF1 and NF2 genes. RESULTS: Thirteen pathogenic variants were identified among the patients, which included one NF1 deletion, three missense variants, three nonsense variants and six frameshifting variants. Among these, 10 variants have been associated with neurofibromatosis type 1. c.4180A>T (p.Asn1394Tyr), c.4217dupT (p.Leu1406fs) and c.1753dupT(p.Leu585Phefs*3) were unreported previously. Based on the guidelines of the American College of Medical Genetics and Genomics, c.4180A>T (p.Asn1394Tyr) was predicted to be likely pathogenic (PS2+PM1+PM2+PP2), while c.4217dupT (p.Leu1406fs) and c.1753dupT (p.Leu585Phefs*3) were predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION Variants of the NF1 gene probably underlay the disease among these children. Above findings have enriched the the spectrum of NF1 gene variants.
Child ; Genes, Neurofibromatosis 1 ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Neurofibromatosis 1/genetics*

Gastrointestinal stromal tumors(GISTs)in the stomach,duodenum,and rectum have low occurrence,and the coexistence GISTs in three parts with neurofibromatosis type Ⅰ(NF-Ⅰ)is even rare.This paper reports a case of GISTs with a family history of NF-Ⅰ.There were multiple nodular masses of different sizes on the patient's face,trunk,and limbs.The patient was admitted due to chest tightness for 5 days and black stools for 1 day.Enhanced CT examination of the abdomen suggested multiple space-occupying lesions in the upper abdomen with multiple small nodules under the abdominal wall,and neurofibromatosis and intestinal stromal tumor cannot be excluded.Finally,surgical pathology confirmed that the multiple tumors in the abdominal cavity were GISTs.The case was confirmed as wild-type GISTs by genetic testing,and the patient recovered well nearly one year after the operation.
Gastrointestinal Stromal Tumors/genetics* ; Humans ; Neurofibromatosis 1/genetics*

OBJECTIVE: To explore the genetic basis for a child with café-au-lait macules and juvenile xanthogranuloma. METHODS: Clinical data and peripheral blood samples of the patient and her family members were collected and subjected to targeted capture and high-throughput sequencing. Candidate variant was verified by Sanger sequencing. RESULTS: A deletional variant in exon 23 of the NF1 gene was detected in the proband. Sanger sequencing has verified it as a de novo variant, which was highly correlated with the clinical manifestations of the patient and her mother. The diagnosis of neurofibromatosis 1 (NF1) was established. The variant was unreported previously. CONCLUSION Targeted capture and next-generation sequencing combined with Sanger sequencing can facilitate early diagnosis of NF1 and provide a basis for the clinical treatment, genetic counseling and prenatal diagnosis.
Child ; Female ; Humans ; Cafe-au-Lait Spots/genetics* ; Genes, Neurofibromatosis 1 ; Neurofibromatosis 1/genetics* ; Xanthogranuloma, Juvenile/genetics*

Child, Preschool ; Humans ; Male ; Neurofibromatosis 1 ; genetics ; Pedigree

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with neurofibromatosis type I (NF1). METHODS: Target capture high-throughput sequencing and Sanger sequencing were carried out to detect the pathological variant in a NF1 patient and his parents. RESULTS: The proband and his similarly affected father have both harbored a novel nonsense variant of c.2511G>A (p.trp837x) in the NF1 gene. The same variant was not found in his mother and 200 healthy controls. CONCLUSION The heterozygous nonsense variant of c.2511G>A (p.trp837x) of the NF1 gene probably underlay the pathogenesis of NF1 in this pedigree.
China ; Heterozygote ; Humans ; Mutation ; Neurofibromatosis 1/genetics* ; Pedigree

Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder caused by NF1 gene mutations. Café au lait spots, neurofibromatosis, Lisch nodules, axillary freckling, dermal neurofibromas and skeletal dysplasia are the most common manifestations for this disease. A 11-year-old boy visited Third Xiangya Hospital, Central South University due to growth-retardation. He was eventually diagnosed as NF1 with growth hormone deficiency. A novel heterozygous splicing mutation c.6579+2 T>C (IVS 34+2 T>C) of NF1 gene was identified in the patient and his mother. Considering NF1 may present with short stature due to growth hormone deficiency, all children with short stature combined with café au lait spots should be screened for NF1, which may assist the clinical diagnosis and the genetic counseling.
Cafe-au-Lait Spots ; diagnosis ; genetics ; Child ; Genes, Neurofibromatosis 1 ; Growth Hormone ; deficiency ; Humans ; Male ; Mutation ; Neurofibromatosis 1 ; blood ; diagnosis

Neurofibromatosis type 1 (NF1) is one of the most commonly inherited autosomal dominant disorders. In order to determine whether genomic alterations and/or chromosomal aberrations involved in the malignant progression of NF1 were present in a Korean patient with NF1, molecular and cytogenetic analyses were performed on the pathologically normal, benign, and malignant tissues and primary cells cultured from those tissues of the patient. The comparative genomic hybridization (CGH) array revealed a Y chromosome loss in the malignant peripheral nerve sheet tumor (MPNST) tissue. G-banding analysis of 50 metaphase cells showed normal chromosomal patterns in the histopathologically normal and benign cultured cells, but a mosaic Y chromosome loss in the malignant cells. The final karyotype for the malignant cells from MPNST tissue was 45,X,-Y[28]/46,XY[22]. The data suggest that the somatic Y chromosome loss may be involved in the transformation of benign tumors to MPNSTs.
Chromosomes, Human, Y/*genetics ; Humans ; Nerve Sheath Neoplasms/*genetics ; Neurofibromatosis 1/*genetics ; Young Adult

OBJECTIVE: To explore the genetic basis for a patient with clinically suspected neurofibromatosis type I, alopecia areata and vitiligo. METHODS: Variant of the NF1 gene was detected by chip capture and high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the family trio. RESULTS: The patient was found to harbor a novel missense c.1885G>A (p.Gly629Arg) variant of the NF1 gene, for which neither parent was carrier. The variant was not recorded in the public database. Based on the guidelines for genetic variation of the American College of Medical Genetics and Genomics, the c.1885G>A missense variant was predicted to be pathogenic (PS1+PS2+PM2+PP3+PP4). CONCLUSION The c.1885G>A missense variant probably underlay the disease in this child. Above finding has enriched the spectrum of the NF1 gene variants.
Alopecia Areata/genetics* ; Child ; Genomics ; Humans ; Mutation ; Neurofibromatosis 1/genetics* ; Vitiligo/genetics*