title: Genetic and clinical mosaicism in a patient with neurofibromatosis type 1.
abstract: Patients with typical features of neurofibromatosis type 1 (NF1) limited to a specific body segment are usually referred to as having "segmental NF1", which is generally assumed to be the result of somatic mosaicism for a NF1 mutation. Mosaicism has also been demonstrated at the molecular level in some sporadic cases with phenotypically classic NF1. In the present report, we describe a patient with NF1 disease manifestations throughout the whole body, but leaving a few sharply delineated segments of the skin unaffected, suggestive of revertant mosaicism. A large intragenic deletion was found by mutation analysis using long-range RT-PCR. The intra-exonic breakpoints were characterized in exon 13 and exon 28, resulting in a deletion of 99,571 bp at the genomic level. The presence of two genetically distinct cell populations, confirming mosaicism for this NF1 mutation, was shown by analysis of several tissues. Revertant mosaicism was excluded by demonstrating heterozygosity for markers residing in the deletion region. The findings in this patient demonstrate two things: (1) although the entire body is affected, mosaicism can still be suspected at clinical examination and proven by DNA analysis and skin biopsies; (2) long-range RT-PCR is a feasible method for demonstrating large intragenic deletions in NF1.
authors: Centre for Medical Genetics, Ghent University Hospital, De Pintelaan 185-0K5, 9000 Ghent, Belgium.
authors: Ina
authors: I
authors: Vandenbroucke
authors: Remco
authors: R
authors: van Doorn
authors: Tom
authors: T
authors: Callens
authors: Jan M
authors: JM
authors: Cobben
authors: Theo M
authors: TM
authors: Starink
authors: Ludwine
authors: L
authors: Messiaen
mesh_terms: D000328:Adult; D001483:Base Sequence; D001706:Biopsy; D004252:DNA Mutational Analysis; D005091:Exons; D005240:Feasibility Studies; D005260:Female; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D009030:Mosaicism / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D012867:Skin / Q000473:pathology
chemical_list: D005819:Genetic Markers