关键词: 咖啡乳斑； DNA突变分析； Legius综合征； SPRED1基因 

Abstract: 【Abstract】 Objective To identify the underlying gene mutation in a family with Legius syndrome mainly manifesting as multiple café-au-lait spots, and to confirm the diagnosis. Methods Clinical data were collected from a proband with multiple café-au-lait spots as the main clinical manifestation, his parents and grandparents. Genomic DNA was extracted from peripheral blood samples of the above subjects. Whole-exome sequencing was performed to identify mutation sites in the proband, PCR and Sanger sequencing were performed to verify the candidate mutation among the family members, and to confirm the diagnosis. Results The proband, a 12-year-old male patient, presented with more than 10 café-au-lait spots with a major diameter of > 5 mm on the trunk, and multiple freckles on the axilla and groin. Mutation analysis of the proband revealed a small heterozygous deletion mutation （c.1220_1238del） in exon 7 of the SPRED1 gene encoding Sprouty-related EVH1 domain-containing protein 1, causing a frameshift mutation in the amino acid sequence （p.L407fs*）. This mutation was detected in the affected mother of the proband, but not in his father or grandparents. The mutation in the proband was a novel mutation, and was inherited from his mother. The mutation was co-segregated with the disease in the family, and a diagnosis of Legius syndrome was made. Conclusion Clinical symptoms of Legius syndrome are similar to those of early-stage neurofibromatosis type Ⅰ, and genetic testing is helpful for early diagnosis, prognosis prediction and follow-up scheduling.

Key words: Cafe-au-Lait spots, DNA mutational analysis, Legius syndrome, SPRED1 gene