A common set of at least 11 functional genes is lost in the majority of NF1 patients with gross deletions.
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.
Jenne
D E
DE
Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Am Klopferspitz 18A, Martinsried, 82152, Germany. djenne@biochem.mpg.de
Tinschert
S
S
Stegmann
E
E
Reimann
H
H
Nürnberg
P
P
Horn
D
D
Naumann
I
I
Buske
A
A
Thiel
G
G
D018929:Cell Culture Techniques; D019457:Chromosome Breakage; D002886:Chromosomes, Human, Pair 17; D020451:Contig Mapping; D003582:Cytogenetics; D005091:Exons; D020224:Expressed Sequence Tags; D005192:Family Health; D017353:Gene Deletion; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017253:Neurofibromatoses / Q000235:genetics / Q000473:pathology; D025542:Neurofibromin 1; D010641:Phenotype; D020161:Physical Chromosome Mapping; D016324:Sequence Tagged Sites
D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1