Mental retardation and cardiovascular malformations in NF1 microdeleted patients point to candidate genes in 17q11.2

NF1 microdeletion syndrome is determined by haploinsufficiency of the NF1 gene and its flanking regions; NF1 microdeleted patients show a more severe phenotype than observed in classical NF1 patients. N The aim of this study was to verify the presence of specific clinical signs of NF1 microdeletion, by combining clinical and genetic evidence from 92 deleted patients, 14 newly characterised and 78 already published. N Statistical analysis, done by comparing the frequency of 10 clinical signs between NF1 microdeleted patients and the whole NF1 population, showed that the most common extra-NF1 clinical signs in microdeleted patients were learning disability, cardiovascular malformations, and dysmorphisms. N Using bioinformatic tools, the deletion gene content of 44 genetically and clinically characterised patients was established. It is proposed that haploinsufficiency of OMG and/or CDK5R1 genes may be implicated in learning disability. In relation to cardiovascular malformations, only JJAZ1 and CENTA2 can be considered as plausible candidate genes. N When present in an NF1 patient, dysmorphisms, cardiac anomalies, and learning disability are signs indicating NF1 microdeletion.