Prenatal Diagnosis in a Fetus With X-Linked Recessive Chondrodysplasia Punctata: Identification and Functional Study of a Novel Missense Mutation in ARSE.
Prenatal Diagnosis in a Fetus With X-Linked Recessive Chondrodysplasia Punctata: Identification and Functional Study of a Novel Missense Mutation in ARSE.
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X 连锁隐性点状软骨发育不良胎儿的产前诊断：ASS 中新型错义突变的鉴定和功能研究
DOI：
10.3389/fgene.2021.722694
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发表时间：
2021
影响因子：
3.7
通讯作者：
Wu L
中科院分区：
文献类型：
--
作者：
Zhang L;Hu H;Liang D;Li Z;Wu L
X连锁隐性斑点软骨发育不良(CDPX1)是一种罕见的骨骼发育不良，其特征为骨痂点状、短指和鼻颌发育不全。CDPX1是由芳基硫酸酯酶E(HASH，又称ARSL)功能丧失引起的。HASH致病突变是新生儿或成人CDPX1的致病基因突变；然而，研究还没有完全探索产前病例。在本研究中，通过全外显子组测序(WES)在一名四肢短小的胎儿中发现了一种新的臀部错义突变(c.265A>；G)。生物信息学分析表明，该变异体是致病的，并对该变异体进行了RT-qPCR、Western印迹和酶分析，以进一步探讨该变异体的致病性。结果表明，该变异体降低了转录和蛋白质表达水平，并导致蛋白质的酶活性丧失。因此，臀部的新突变c.265A和gt；G是胎儿表现出表型的遗传原因。本研究利用HASH的功能分析，在中国人群中发现了一例产前病例，有助于家庭预测未来妊娠的复发风险，并为了解这种罕见的疾病提供更多的信息。结果表明，WES是一种可行的CDPX1胎儿产前诊断方法。
X-Linked recessive chondrodysplasia punctata (CDPX1) is a rare skeletal dysplasia characterized by stippled epiphyses, brachytelephalangy, and nasomaxillary hypoplasia. CDPX1 is caused by function loss of arylsulfatase E (ARSE, also known as ARSL). Pathogenic mutations in ARSE are responsible for CDPX1 in newborns or adults; however, studies have not fully explored prenatal cases. In the current study, a novel missense mutation (c.265A > G) in ARSE was identified in a fetus with short limbs using whole-exome sequencing (WES). Bioinformatic analysis showed that the variant was pathogenic, and RT-qPCR, Western blot, and enzymatic assays were performed to further explore pathogenicity of the variant. The findings showed that the variant decreased transcription and protein expression levels and led to loss of enzymatic activity of the protein. The novel mutation c.265A > G in ARSE was thus the genetic cause for the phenotype presented by the fetus. The current study presents a prenatal case in Chinese population using functional analysis of ARSE, which helps the family to predict recurrence risks for future pregnancies and provides more information for understanding this rare condition. The findings show that WES is a feasible method for prenatal diagnosis of fetuses with CDPX1.
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影响因子：
8.8
作者：
Matos-Miranda, Claudia;Nimmo, Graeme;Braverman, Nancy
通讯作者：
Braverman, Nancy
DOI：
10.1001/archotol.130.12.1423
发表时间：
2004-12-01
影响因子：
--
作者：
Wolpoe, ME;Braverman, N;Lin, SY
通讯作者：
Lin, SY
影响因子：
3.5
作者：
Sardiello, M;Annunziata, I;Ballabio, A
通讯作者：
Ballabio, A
影响因子：
2
作者：
Li, Ruibing;Wang, Jianan;Wang, Chengbin
通讯作者：
Wang, Chengbin
DOI：
10.1016/j.bbadis.2004.09.003
发表时间：
2004-12-24
影响因子：
6.2
作者：
Ghosh, D
通讯作者：
Ghosh, D