Abstract：
Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome is a rare genodermatosis characterized by a classic triad of follicular ichthyosis, alopecia, and photophobia. We report a Chinese patient displaying features of IFAP triad along with painful palmoplantar keratoderma, recurrent infections, periorificial keratotic plaques, nail dystrophy, and pachyonychia. Whole-exome sequencing revealed an intronic variant (NM_015884.3: exon7:c.970+5G>A) in the gene MBTPS2. Sanger sequencing confirmed that the variant segerated with phenotype in the family. Sequencing of cDNAs derived from the patient indicated the variant introduced a new splice donor site, leading to partial skipping of exon 7 (r.951_970del). An in vitro mini-gene assay also revealed abnormal splicing of exon 7. This study presents a case complicated with X-linked IFAP syndrome and Olmsted syndrome, and highlights the significance of using validation assays to identify the pathogenicity of intronic variants in MBTPS2.
摘要：
毛囊鱼鳞病伴萎缩性和畏光综合征（IFAP）是一种罕见的遗传性皮肤病，其特征是滤泡性鱼鳞病的经典三联征，脱发,和畏光。我们报告了一名中国患者，表现出IFAP三联征的特征以及疼痛的掌plant角化病，反复感染,骨周角化斑块，指甲营养不良,和白甲。全外显子组测序揭示了基因MBTPS2中的内含子变体(NM_015884.3:外显子7:c.970+5G>A)。Sanger测序证实该变体在该家族中具有表型。来自患者的cDNA测序表明该变体引入了新的剪接供体位点，导致外显子7的部分跳跃（r.951_970del）。体外微型基因测定也显示外显子7的异常剪接。这项研究提出了一例X连锁IFAP综合征和Olmsted综合征，并强调了使用验证测定法来鉴定MBTPS2中内含子变体的致病性的重要性。
