Question: Mutation of which gene and which chromosome cause Neurofibromatosis type I?

Context:
The von Recklinghausen neurofibromatosis (NF1) gene has been localized to the pericentromeric region of chromosome 17.
Nine markers from the pericentromeric region of chromosome 17 were typed in 16 British and five South African families with neurofibromatosis type 1 (NF1).
Inspection of recombinant events in families informative for several markers suggests that the NF1 gene is located between the markers EW301 (cen-p11.2) and EW206 (cen-q12) and possibly distal to pHHH202 (q11.2-q12).
The gene for von Recklinghausen neurofibromatosis type 1 (NF1) has recently been mapped to the pericentromeric region of human chromosome 17.
In addition to reporting, in accompanying papers, their individual analyses of mapping the neurofibromatosis type 1 (NF1) gene on chromosome 17, members of the International Consortium for NF1 Linkage contributed their data for our joint analysis to determine the exact sequence of flanking markers and to obtain precise estimates and confidence limits of the recombination fractions for the closest markers, in anticipation of clinical use.
To better map the location of the von Recklinghausen neurofibromatosis (NF1) gene, we have characterized a somatic cell hybrid designated 7AE-11. This microcell-mediated, chromosome-transfer construct harbors a centromeric segment and a neo-marked segment from the distal long arm of human chromosome 17.
The cosmids in the NF1 region will be an important resource for testing DNA blots of large-fragment restriction-enzyme digests from NF1 patient cell lines, to detect rearrangements in patients' DNA and to identify the 17;22 NF1 translocation breakpoint.
The frequent LOH surrounding the NF1 locus and lack of neurofibromin expression in these tumors suggest that NF1 gene mutations may contribute to the development of adrenal gland neoplasms in patients with NF1.
In the latter, the breakpoint in 17q occurred below the centromere and is at or in the region of the Neurofibromatosis Type 1 (NF1) gene.
Neurofibromatosis type I (NF1) is an autosomal dominant condition associated with mutations in the long arm of chromosome 17, and characterised by neurofibromas, café-au-lait spots and axillary freckling.
In addition, the mother's and maternal grandmother's genetic analysis showed identical mutations in the neurofibromatosis I gene on the long arm of chromosome 17, confirming the diagnosis of NF1.
Duplicon-mediated microdeletions around the NF1 gene are frequently associated with a severe form of neurofibromatosis type I in a subgroup of patients who show an earlier onset of cutaneous neurofibromas, dysmorphic facial features, and lower IQ values.
Neurofibromatosis had been diagnosed in infancy, and genetic testing showed that the patient had a mutation in chromosome 17, consistent with neurofibromatosis type I.
Neurofibromatosis Type 1 (NF1) is one of the most common inherited diseases in humans. It is caused by a mutation in the NF1 gene on chromosome 17, and is associated with numerous central and peripheral nervous system manifestations.
In 95% of NF1 individuals, a mutation is found in the NF1 gene, and in 5% of the patients, the germline mutation consists of a microdeletion that includes the NF1 gene and several flanking genes.
Herein, we describe a unique case of anaplastic de novo astroblastoma-sarcoma, in essence a variant of gliosarcoma, occurring in a 50-year-old female with documented NF1. Genetic study (fluorescence in situ hybridization) demonstrated no chromosomal losses or gains. Testing for abnormalities of chromosomes 7, 9, 10, 12, 17, 19 and 20, including the EGFR, p16, PTEN, MDM2 and NF1 gene regions, we found the tumor to exhibit a deletion of PTEN, monosomy 17 and gains of chromosomes 19 and 20q.
Neurofibromatosis type I (NF1) is an autosomal dominant disorder affecting 1 in 3000 people. The NF1 gene is located on chromosome 17q11.2, spans 350 kb of genomic DNA, and contains 60 exons.
A patient with recurrent-remittent multiple sclerosis associated with neurofibromatosis type I is described. The case is interesting for two reasons: 1) the difficulty of evaluating MRI findings, since both entities involve similar anomalies and 2) the relation between the two entities, according to evidence from recent genetic studies showing that the myelin protein gene associated to oligodendrocytes is part of an intron of the neurofibromatosis-1 gene of chromosome 17.
Neurofibromatosis type I (NFI) is a common autosomal dominant disorder with an increased risk for developing benign and malignant tumors. The NFI gene has been cloned and maps to 17q11.2, and the gene product acts as a tumor suppressor gene.
Direct sequencing of the NF1 gene in tumor DNA identified the presence of an inactivating NF1 somatic mutation in 41% (25/61) of analyzed sporadic tumors, associated with loss of the wild-type allele in 84% (21/25) of cases.
A novel mutation c.4821delA was identified in NF1 gene, which predicted truncation of neurofibromin (p.Leu1607fs).
She had a genotype of heterozygous c.6709C>T mutation of NF1 gene.
RESULTS: The mutational analysis of the NF1 gene revealed a novel frameshift insertion mutation in exon 4c (c.654 ins A) in all affected family members.
Using lymphoblastoid, fibroblast, and buccal cell samples collected from both twins and from other family members in three generations, we discovered a pathogenic nonsense mutation in exon 40 of the NF1 gene.
We also found a novel non-synonymous change in exon 16 of the NF1 gene that was transmitted from the unaffected mother to both twins and co-segregated with the pathogenic mutation in the ensuing generation.
The disease gene of the Chinese NF1 family was linked to NF1 locus, and a nonsense mutation, G1336X in the NF1 gene was identified.
The present study demonstrated that G1336X mutation in the NF1 gene cause Neurofibromatosis type I in the family.

Answer: Neurofibromatosis Type I is an autosomal dominant condition associated with NF-1 gene mutation that is located in the long arm of chromosome 17 (17q11.2). In the majority (95%) of Neurofibromatosis Type I individuals, the mutation is found in the NF1 gene, while the remaining 5% of the patients have different types of genetic abnormalities.

Exact answer: NF1 gene, chromosome 17