Elsevier

Genomics

Volume 66, Issue 1, 15 May 2000, Pages 93-97
Genomics

Short Communication
A Common Set of at Least 11 Functional Genes Is Lost in the Majority of NF1 Patients with Gross Deletions

https://doi.org/10.1006/geno.2000.6179Get rights and content

Abstract

Large deletions of the NF1 locus occur in 5 to 10% of patients with neurofibromatosis and are commonly associated with specific additional abnormalities characterized by mental retardation, dysmorphic features, and intellectual impairment. To characterize the extent of codeleted genes we constructed a long-range physical BAC/PAC map around the NF1 locus between D17S117 and D17S57 and determined the deletion boundaries in seven unrelated patients. Surprisingly, the proximal and distal breakpoints in five of seven patients fall at almost identical positions, resulting in the loss of at least 11 functional genes. Five of six patients investigated showed a de novo deletion on the maternally derived chromosome. Since D17S117 and D17S57 were previously reported as the outer limits for the great majority of NF1 deletions, we suggest that most NF1 patients with deletion of the entire NF1 gene are hemizygous for the same set of at least 10 additional genes, including SHGC-37343, SHGC-2390, SHGC-34232, OMG, EVI2B, EVI2A, WI-9521, WI-6742, SHGC-34334, and KIAA0160, and thus present with a relatively uniform clinical phenotype.

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Cited by (34)

  • Neurofibromatosis type 2 and multiple sclerosis

    2020, Multiple Sclerosis and Related Disorders
    Citation Excerpt :

    An association between Neurofibromatosis type 1 and the development of MS has been previously described (Etemadifar et al., 2009). Patients with large deletions in the NF1 gene have a loss of a common set of 11 functional genes, including the loss of the OMG gene, encoding the oligodendrocyte myelin glycoprotein which lies in an intron of the NF1 gene (Jenne et al., 2000,). However, this specific mutation is not a prerequisite to develop MS (Johnson et al., 2000), therefore a genetic association between these two diseases can be excluded.

  • High frequency of mosaicism among patients with neurofibromatosis type 1 (NF1) with microdeletions caused by somatic recombination of the JJAZ1 gene

    2004, American Journal of Human Genetics
    Citation Excerpt :

    In the adult mouse brain, Jjaz1 is highly expressed in the hippocampus, the pyriform cortex, the habenula, the granular cell layer of the cerebellum, and the surrounding Purkinje cells (fig. 5B and 5D). Previous studies showed that, in ∼50% of NF1 microdeletions, the breakpoints are located in the NF1 LCRs (López Correa et al. 1999, 2001; Dorschner et al. 2000; Jenne et al. 2000, 2001). In our sample, 13 (62%) of 21 deletions have breakpoints in the NF1 LCRs (table 2).

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Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession Nos. AJ272195, AJ272196, AJ272197.

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