Zeng Lei, Jin Jie-Yuan, Luo Fang-Mei, Sheng Yue, Wu Pan-Feng, Xiang Rong
Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
School of Life Sciences, Central South University, Changsha, China.
Front Pediatr. 2022 May 16;10:797978. doi: 10.3389/fped.2022.797978. eCollection 2022.
Preaxial polydactyly (PPD) is a common congenital abnormality with an incidence of 0.8-1.4% in Asians, characterized by the presence of extra digit(s) on the preaxial side of the hand or foot. PPD is genetically classified into four subtypes, PPD type I-IV. Variants in six genes/loci [including GLI family zinc finger 3 (), ZPA regulatory sequence (ZRS), and pre-ZRS region] have been identified in PPD cases. Among these loci, ZRS is, perhaps, the most special and well known, but most articles only reported one or a few cases. There is a lack of reports on the ZRS-variant frequency in patients with PPD. In this study, we recruited 167 sporadic or familial cases (including 154 sporadic patients and 13 families) with PPD from Central-South China and identified four ZRS variants in four patients (2.40%, 4/167), including two novel variants (ZRS131A > T/chr7:g.156584439A > T and ZRS474C > G/chr7:g.156584096C > G) and two known variants (ZRS428T > A/chr7:g.156584142T > A and ZRS619C > T/chr7:g.156583951C > T). ZRS131A > T and ZRS428T > A were detected in PPD I cases and ZRS474C > G and ZRS619C > T combinedly acted to cause PPD II. The detectable rate of ZRS variants in PPD I was 1.60% (2/125), while PPD II was significantly higher (9.52%, 2/21). Three bilateral PPD cases harbored ZRS variants (13.64%, 3/22), suggesting that bilateral PPD was more possibly caused by genetic etiologies. This study identified two novel ZRS variants, further confirmed the association between ZRS and PPD I and reported a rare PPD II case resulted from the compound heterozygote of ZRS. This investigation preliminarily evaluated a ZRS variants rate in patients with PPD and described the general picture of PPD in Central-South China.
轴前多指畸形（PPD）是一种常见的先天性异常，在亚洲人群中的发病率为0.8 - 1.4%，其特征是在手或脚的轴前侧出现多指。PPD在遗传学上分为四种亚型，即PPD I - IV型。在PPD病例中已鉴定出六个基因/位点的变异[包括GLI家族锌指蛋白3（）、ZPA调控序列（ZRS）和前ZRS区域]。在这些位点中，ZRS可能是最特殊且最知名的，但大多数文章仅报道了一两个病例。目前缺乏关于PPD患者中ZRS变异频率的报道。在本研究中，我们从中国中南地区招募了167例散发性或家族性PPD病例（包括154例散发性患者和13个家系），并在4例患者（2.40%，4/167）中鉴定出4个ZRS变异，包括2个新变异（ZRS131A > T/chr7:g.156584439A > T和ZRS474C > G/chr7:g.156584096C > G）以及2个已知变异（ZRS428T > A/chr7:g.156584142T > A和ZRS619C > T/chr7:g.156583951C > T）。ZRS131A > T和ZRS428T > A在PPD I型病例中被检测到，而ZRS474C > G和ZRS619C > T共同作用导致PPD II型。PPD I型中ZRS变异的检出率为1.60%（2/125），而PPD II型则显著更高（9.52%，2/21）。3例双侧PPD病例携带ZRS变异（13.64%，3/22），表明双侧PPD更可能由遗传病因引起。本研究鉴定出2个新的ZRS变异，进一步证实了ZRS与PPD I型之间的关联，并报道了1例由ZRS复合杂合子导致的罕见PPD II型病例。本调查初步评估了PPD患者中ZRS变异率，并描述了中国中南地区PPD的总体情况。
