Nagashima-type palmoplantar keratoderma (NPPK) is characterized by non-progressive, diffuse, and cross-gradient hyperkeratosis caused by mutations in the SERPINB7 gene on chromosome 18q21.33. Chromosome 18q deletion syndrome (18q- syndrome) is a terminal deletion or microdeletion syndrome characterized by intellectual disability and congenital malformations. This paper describes an 18-year-old man with palmoplantar keratoderma and diffuse white matter abnormalities in the brain. Trio-based exome sequencing (ES) revealed a suspected mosaic compound heterozygous mutation for c.796C>T (p.Arg266^∗) in exon 8 inherited from the mother and a de novo exons 4–6 deletion of SERPINB7. Additional copy number variant (CNV) analysis of the ES data indicated a heterozygous gross deletion of 18q22.3-q23. The two SERPINB7 gene variants were verified by Sanger sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Finally, low-coverage whole-genome sequencing (WGS) confirmed the 18q22.3-q23 deletion and additionally detected a mosaic 18q21.33-q22.3 deletion, together explaining NPPK and the neurological phenotypes of the proband. The gross deletion of all exons of SERPINB7 was revealed for the first time. More rarely, c.796C>T (p.Arg266^∗) was likely to be mosaic, while the exon deletion was mosaic. In conclusion, the combination of multiple molecular genetic testing methods provides comprehensive informative molecular findings and promotes the diagnosis of complex diseases, as in this case.

长岛型掌跖角化病 (NPPK) 的特征是非进行性、弥漫性和交叉梯度角化过度，由 SERPINB7染色体 18q21.33 上的基因。染色体18q缺失综合征（18q-综合征）是一种以智力障碍和先天畸形为特征的终末缺失或微缺失综合征。本文描述了一名患有掌跖角化病和大脑弥漫性白质异常的 18 岁男子。基于三重组的外显子测序 (ES) 揭示了从母亲遗传的外显子 8 中c.796C>T (p.Arg266 ^* )的疑似嵌合复合杂合突变，以及从头开始 外显子 4-6 缺失 SERPINB7. ES 数据的额外拷贝数变异 (CNV) 分析表明 18q22.3-q23 的杂合总体缺失。他们俩SERPINB7通过 Sanger 测序和定量实时聚合酶链反应 (qRT-PCR) 验证基因变异。最后，低覆盖全基因组测序 (WGS) 证实了 18q22.3-q23 缺失，并另外检测到镶嵌 18q21.33-q22.3 缺失，共同解释了 NPPK 和先证者的神经表型。所有外显子的严重缺失SERPINB7第一次被揭露。更罕见的是，c.796C>T (p.Arg266 ^* ) 可能是嵌合体，而外显子缺失是嵌合体。总之，多种分子遗传学检测方法的结合提供了全面的信息分子发现并促进了复杂疾病的诊断，如本例。