In affected members of a 5-generation family with neurofibromatosis-Noonan syndrome (NFNS; 601321), Nystrom et al. (2009) identified a heterozygous 4168C-T transition in exon 24 of the NF1 gene, resulting in a leu1390-to-phe (L1390F) substitution in the highly conserved GAP-related domain. The family was originally reported by Edman Ahlbom et al. (1995) as having Noonan syndrome based on dysmorphic facial features, short stature, pulmonary stenosis, and short neck. Upon reevaluation, Nystrom et al. (2009) found that several family members had cafe-au-lait spots, axillary freckling, Lisch nodules, and multiple nevi, consistent with NF1, but that all family members lacked dermal and superficial plexiform neurofibromas. The authors concluded that the clinical diagnosis was consistent with NFNS. Nystrom et al. (2009) postulated that the L1390F mutation resulted in impaired GTPase activity.
