Abstract: Objective: To conduct histological and blood genetic testing on 16 patients admitted for segmental café-au-lait spots, clarify the spectrum of pathogenic genes, and provide evidence-based support for clinical diagnosis and differential diagnosis. Methods: Genomic DNA was extracted from the blood samples and lesional skin tissues of the 16 patients as well as their unaffected family members (parents); relevant pathogenic genes were detected via whole-exome sequencing, and the reliability of the identified pathogenic genes was verified by bidirectional Sanger sequencing. Results: Clinically relevant pathogenic mutations were detected in 10 patients: 1 case carried the RAF1 gene c.55G＞A mutation and was diagnosed with Noonan syndrome; 7 cases harbored NF1 gene mutations including c.3897del, c.6789_6792delTTAC, c.1885G＞A, c.1721G＞A, c.479+28C＞T, c.6207dup and exon1-57 del, respectively, and were diagnosed with segmental neurofibromatosis type 1; 1 case had the SPRED1 gene c.881A＞T mutation and was diagnosed with Legius syndrome; another case carried the GNAS gene c.1906G＞A mutation and was diagnosed with McCune-Albright syndrome. No clinically relevant pathogenic mutations were identified in the remaining 6 patients. Conclusion: All 16 patients in this study presented with segmental café-au-lait spots, and different gene mutations were detected through genetic testing; therefore, the diagnosis of such diseases should be comprehensively determined based on the combination of clinical manifestations and genetic testing results.

Key words: segmental café-au-lait spots, Noonan syndrome, segmental neurofibromatosis, Legius syndrome, McCune-Albright syndrome, gene mutation