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CFAP47 基因突变也与 PCD 患者的呼吸缺陷有关，该基因先前被报道为 MMAF 的致病基因。

Mutations in CFAP47, a previously reported MMAF causative gene, also contribute to the respiratory defects in patients with PCD.

机构信息

McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

出版信息

Mol Genet Genomic Med. 2024 Jan;12(1):e2278. doi: 10.1002/mgg3.2278. Epub 2023 Sep 18.

DOI:10.1002/mgg3.2278
PMID:37723893
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10767284/
Abstract

BACKGROUND

Primary ciliary dyskinesia (PCD) is a genetic ciliopathy characterized by dysfunction of motile cilia. Currently, approximately 50 causative genes accounting for 60%-70% of all PCD cases have been identified in PCD-affected individuals, but the etiology in approximately 30%-40% of PCD cases remains unknown.

METHODS

We analyzed the clinical and genetic data of two PCD individuals who were suspected of having PCD. Whole-exome sequencing and Sanger sequencing were performed to identify and verify the variants in CFAP47. We also evaluated the expression of CFAP47 by real-time quantitative PCR and immunofluorescence. Transmission electron microscopy in respiratory epithelial cells was also conducted to analyze ciliary function.

RESULTS

Two hemizygous missense variants of X-linked CFAP47 in two unrelated PCD individuals were identified. The expression of CFAP47 in two PCD individuals was significantly reduced in vivo and in vitro assays. A reduction in the amount of epithelial ciliary cells and basal bodies from PCD individuals was also observed.

CONCLUSIONS

We describe two hemizygous missense variants of X-linked CFAP47 in two unrelated PCD individuals and prove CFAP47 variants are related to a reduced number of epithelial ciliary cells. Therefore, we suggest that CFAP47 should be known as a novel pathogenic gene of human PCD.

摘要

背景

原发性纤毛运动障碍（PCD）是一种以运动纤毛功能障碍为特征的遗传性纤毛病。目前，在 PCD 患者中已发现约 50 个致病基因，占所有 PCD 病例的 60%-70%，但仍有约 30%-40%的 PCD 病例病因不明。

方法

我们分析了两名疑似患有 PCD 的 PCD 个体的临床和遗传数据。进行全外显子组测序和 Sanger 测序以鉴定和验证 CFAP47 中的变体。我们还通过实时定量 PCR 和免疫荧光评估 CFAP47 的表达。还进行了呼吸道上皮细胞的透射电子显微镜检查以分析纤毛功能。

结果

在两名无关联的 PCD 个体中发现了 X 连锁 CFAP47 的两个半合子错义变异。在体内和体外试验中，两名 PCD 个体的 CFAP47 表达明显降低。还观察到 PCD 个体的上皮纤毛细胞和基体数量减少。

结论

我们在两名无关联的 PCD 个体中描述了 X 连锁 CFAP47 的两个半合子错义变异，并证明 CFAP47 变异与上皮纤毛细胞数量减少有关。因此，我们建议将 CFAP47 视为人类 PCD 的一种新的致病基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d058/10767284/8360982e223d/MGG3-12-e2278-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d058/10767284/f360664a1ee6/MGG3-12-e2278-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d058/10767284/2529df606fc3/MGG3-12-e2278-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d058/10767284/44665e0b27fa/MGG3-12-e2278-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d058/10767284/8360982e223d/MGG3-12-e2278-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d058/10767284/f360664a1ee6/MGG3-12-e2278-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d058/10767284/2529df606fc3/MGG3-12-e2278-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d058/10767284/44665e0b27fa/MGG3-12-e2278-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d058/10767284/8360982e223d/MGG3-12-e2278-g002.jpg

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