Abstract：
Setleis syndrome (SS), or focal facial dermal dysplasia type III (FFDD3, MIM #227260), is an autosomal recessive condition caused by biallelic loss-of-function variants in TWIST2. It is characterized by bitemporal atrophic skin lesions and distinctive facial features. Individuals with de novo or inherited duplication or triplication of the chromosomal region 1p36.22p36.21 have also been reported to have the SS phenotype with additional neurodevelopmental challenges (rarely seen in individuals with TWIST2 mutations) and variable expressivity and penetrance. Triplication of this region is also associated with more severe manifestations compared to a duplication. We report a 2-year-old female patient with features of SS associated with a de novo 3.603 Mb triplication at 1p36.23p36.22 identified on postnatal microarray analysis. Her triplication shares a 281.263 kb overlap with gains at 1p36.22, reported by previous groups, delineating the shortest region of overlap (SRO) to date. This SRO involves 10 RefSeq and 4 OMIM morbid map genes and highlights the candidate dosage-sensitive element(s) underlying the cardinal features of SS phenotype in individuals with gains at 1p36.
摘要：
Setleis综合征（SS），或局灶性面部真皮发育不良III型（FFDD3，MIM#227260），是由TWIST2中的双等位基因功能丧失变体引起的常染色体隐性条件。它的特点是双颞叶萎缩性皮肤病变和独特的面部特征。据报道，染色体区域1p36.22p36.21的从头或遗传重复或三倍体的个体也具有SS表型，具有额外的神经发育挑战（在具有TWIST2突变的个体中很少见）以及可变的表达和外显率。与重复相比，该区域的三重复也与更严重的表现有关。我们报告了一名2岁女性患者，其SS的特征与在出生后微阵列分析中发现的1p36.23p36.22的从头3.603Mb三重复相关。根据先前小组的报告，她的三倍重叠为281.263kb，收益为1p36.22，划定迄今为止最短重叠区域(SRO)。该SRO涉及10个RefSeq和4个OMIM病态图谱基因，并突出显示了在1p36处获得的个体中SS表型的主要特征的候选剂量敏感元件。
