title: Diagnostic value of multiple café-au-lait macules for neurofibromatosis 1 in Chinese children.
abstract: Neurofibromatosis 1 (NF1) is a common autosomal dominant condition caused by mutations in the NF1 gene. The appearance of multiple café-au-lait macules is an early sign of the condition, which often alert physicians to follow up and further examine the patient for the possibility of NF1. In order to determine the predictive value of multiple café-au-lait macules at early age for NF1 in Chinese patients, we recruited 19 children who shared the common sign of multiple café-au-lait macules from a general pediatric clinic in Shanghai. All the patients were clinically evaluated following the National Institutes of Health criteria for NF1 and molecular tested for sequence variants and copy number changes. Nine children met the clinical diagnostic criteria of NF1, and molecular tests confirmed all nine patients with pathogenic variants including two genomic deletions, two novel frame-shift variants, four novel nonsense and a splicing variants. In addition, four children who did not meet the diagnostic criteria were also found to carry pathogenic NF1 variants. Overall, 68.4% (13/19) of children with café-au-lait macules and various other clinical presentations were molecularly confirmed with NF1. This study demonstrated that the majority of Chinese children with multiple café-au-lait macules who came to seek for medical attention had NF1. Molecular testing is necessary to be used as an adjunct and sometimes as the main tool for confirming and diagnosing children of NF1 at early age.
authors.affiliation: Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ruen
authors.initials: R
authors.lastname: Yao
authors.affiliation: Xinhua Hospital, Institute for Pediatric Research, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Xinhua Hospital, Institute for Pediatric Research, Shanghai, China.
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Boston Children's Hospital, Boston, Massachusetts, USA.|Claritas Genomics, Cambridge, Massachusetts, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D019080:Cafe-au-Lait Spots / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D018389:Codon, Nonsense; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D046228:Microarray Analysis; D009456:Neurofibromatosis 1 / Q000175:diagnosis* / Q000235:genetics; D025542:Neurofibromin 1 / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense; D025542:Neurofibromin 1
keywords: café-au-lait macules; clinical diagnosis; deletion; molecular diagnosis; neurofibromatosis 1; sequence variant