Neurofibromatosis type 1
(NF1) is the most common autosomal dominant neurocutaneous syndrome with the
estimated prevalence ranging from 1 in 3000 to 1 in 4000 individuals and wide
phenotypical variability. NF1 is caused by autosomal dominant heterozygous
mutations in the neurofibromin gene which is located on the chromosome 17
(17q11.2). Phenotypically, NF1 patients have a very heterogeneous clinical
phenotype. In this study, a novel frameshift NF1 variant was identified in a
Croatian family with NF1 (mother and two daughters). The novel variant c.
4482_4483delTA leads to sequence change that creates a premature translational
stop signal (p.His1494Glnfs*7) in the NF1 gene. Our study showed that even when
the same germline NF1 variant has been identified, there is still huge phenotypic
variability in patients even within the same family, and it makes prognosis of
the disease more complex. The development of next-generation sequencing
technologies which allow rapid and accurate identification of disease-causing
mutations becomes crucial for molecular characterization of NF1 patients as
well as for patient follow-up, in the context of genetic counseling and
clinical management of patients.
Five novel
NF1
gene pathogenic variants in 10 different Chinese families with neurofibromatosis type 1
