PURPOSE: Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder 
with an estimated incidence of one in 3,500 births. Clinically, NF1 is 
characterized by café-au-lait (CAL) spots, neurofibromas, freckling of the 
axillary or inguinal region, Lisch nodules, optic nerve glioma, and bone 
dysplasias. NF1 is caused by inactivating mutations of the 17q11.2-located NF1 
gene. We present a clinical and molecular study of an Italian family with NF1.
METHODS: The proband, a 10-year-old boy, showed large CAL spots and freckling on 
the axillary region and plexiform neurofibromas on the right side only. His 
father (47 years old) showed, in addition to the similar signs, numerous 
neurofibromas of various sizes on his thorax, abdomen, back, and shoulder. Two 
additional family members (a brother and a sister of the proband) presented only 
small CAL spots. The coding exons of NF1 gene were analyzed for mutations by 
denaturing high-performance liquid chromatography and sequencing in all family 
members.
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. This 
novel mutation creates a shift on the reading frame starting at codon 218 and 
leads to the introduction of a premature stop at codon 227.
CONCLUSIONS: The segregation of the mutation with the affected phenotype and its 
absence in the 200 normal chromosomes suggest that it is responsible for the NF1 
phenotype.