Identification of Two Novel DNAAF2 Variants in Two Consanguineous Families with Primary Ciliary Dyskinesia

Chenyang Lu,1– 3,* Danhui Yang,1– 3,* Cheng Lei,1– 3 Rongchun Wang,1– 3 Ting Guo,1– 3 Hong Luo1– 3 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, People’s Repu...

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Autores principales:	Lu C, Yang D, Lei C, Wang R, Guo T, Luo H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	primary ciliary dyskinesia scoliosis dnaaf2 bronchiectasis situs inversus female infertility Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/062f630993744098a407cf3c5011bebe
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spelling	oai:doaj.org-article:062f630993744098a407cf3c5011bebe2021-11-11T18:22:26ZIdentification of Two Novel DNAAF2 Variants in Two Consanguineous Families with Primary Ciliary Dyskinesia1178-7066https://doaj.org/article/062f630993744098a407cf3c5011bebe2021-11-01T00:00:00Zhttps://www.dovepress.com/identification-of-two-novel-dnaaf2-variants-in-two-consanguineous-fami-peer-reviewed-fulltext-article-PGPMhttps://doaj.org/toc/1178-7066Chenyang Lu,1– 3,* Danhui Yang,1– 3,* Cheng Lei,1– 3 Rongchun Wang,1– 3 Ting Guo,1– 3 Hong Luo1– 3 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, People’s Republic of China; 3Hunan Diagnosis and Treatment Center of Respiratory Disease, Changsha, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Hong Luo; Ting GuoDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Furong District, Changsha, Hunan, 410011, People’s Republic of ChinaEmail luohonghuxi@csu.edu.cn; guotingxy@csu.edu.cnBackground: Dynein axonemal assembly factor 2 (DNAAF2) is involved in the early preassembly of dynein in the cytoplasm, which is essential for motile cilia function. Primary ciliary dyskinesia (PCD) associated with DNAAF2 variants has rarely been reported in females with infertility. Moreover, there is no report linking DNAAF2 to scoliosis in human.Materials and Methods: We recruited patients from two consanguineous families with a clinical diagnosis of PCD and collected their clinical history, laboratory tests, and radiographic data. Sequencing and bioinformatics analysis were then performed. Immunofluorescence and high-speed microscope analysis were used to support the pathogenicity of the variant.Results: Proband 1, a 26-year-old female from family I, exhibited scoliosis, bronchiectasis, sinusitis, situs inversus, and infertility. We found a novel homozygous missense variant in DNAAF2, c.491T>C, p.(Leu164Pro) in this patient. Subsequent immunofluorescence indicated the absence of outer dynein arm and inner dynein arm of cilia, and high-speed microscopy analysis showed that the most of the cilia are static, which support the pathogenicity of this variant. Proband 2, a 53-year-old female, presented with bronchiectasis, sinusitis, and infertility. In this patient, a new homozygous frameshift variant DNAAF2, c.822del, p.(Ala275Profs10) was identified. The disease-causing variants mentioned above are not included in the current authorized genetic databases.Conclusion: Our findings expand the spectrum of DNAAF2 variants and link DNAAF2 to female infertility and likely scoliosis in patients with PCD.Keywords: primary ciliary dyskinesia, scoliosis, DNAAF2, bronchiectasis, situs inversus, female infertilityLu CYang DLei CWang RGuo TLuo HDove Medical Pressarticleprimary ciliary dyskinesiascoliosisdnaaf2bronchiectasissitus inversusfemale infertilityTherapeutics. PharmacologyRM1-950ENPharmacogenomics and Personalized Medicine, Vol Volume 14, Pp 1415-1423 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	primary ciliary dyskinesia scoliosis dnaaf2 bronchiectasis situs inversus female infertility Therapeutics. Pharmacology RM1-950
spellingShingle	primary ciliary dyskinesia scoliosis dnaaf2 bronchiectasis situs inversus female infertility Therapeutics. Pharmacology RM1-950 Lu C Yang D Lei C Wang R Guo T Luo H Identification of Two Novel DNAAF2 Variants in Two Consanguineous Families with Primary Ciliary Dyskinesia
description	Chenyang Lu,1– 3,* Danhui Yang,1– 3,* Cheng Lei,1– 3 Rongchun Wang,1– 3 Ting Guo,1– 3 Hong Luo1– 3 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, People’s Republic of China; 3Hunan Diagnosis and Treatment Center of Respiratory Disease, Changsha, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Hong Luo; Ting GuoDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Furong District, Changsha, Hunan, 410011, People’s Republic of ChinaEmail luohonghuxi@csu.edu.cn; guotingxy@csu.edu.cnBackground: Dynein axonemal assembly factor 2 (DNAAF2) is involved in the early preassembly of dynein in the cytoplasm, which is essential for motile cilia function. Primary ciliary dyskinesia (PCD) associated with DNAAF2 variants has rarely been reported in females with infertility. Moreover, there is no report linking DNAAF2 to scoliosis in human.Materials and Methods: We recruited patients from two consanguineous families with a clinical diagnosis of PCD and collected their clinical history, laboratory tests, and radiographic data. Sequencing and bioinformatics analysis were then performed. Immunofluorescence and high-speed microscope analysis were used to support the pathogenicity of the variant.Results: Proband 1, a 26-year-old female from family I, exhibited scoliosis, bronchiectasis, sinusitis, situs inversus, and infertility. We found a novel homozygous missense variant in DNAAF2, c.491T>C, p.(Leu164Pro) in this patient. Subsequent immunofluorescence indicated the absence of outer dynein arm and inner dynein arm of cilia, and high-speed microscopy analysis showed that the most of the cilia are static, which support the pathogenicity of this variant. Proband 2, a 53-year-old female, presented with bronchiectasis, sinusitis, and infertility. In this patient, a new homozygous frameshift variant DNAAF2, c.822del, p.(Ala275Profs10) was identified. The disease-causing variants mentioned above are not included in the current authorized genetic databases.Conclusion: Our findings expand the spectrum of DNAAF2 variants and link DNAAF2 to female infertility and likely scoliosis in patients with PCD.Keywords: primary ciliary dyskinesia, scoliosis, DNAAF2, bronchiectasis, situs inversus, female infertility
format	article
author	Lu C Yang D Lei C Wang R Guo T Luo H
author_facet	Lu C Yang D Lei C Wang R Guo T Luo H
author_sort	Lu C
title	Identification of Two Novel DNAAF2 Variants in Two Consanguineous Families with Primary Ciliary Dyskinesia
title_short	Identification of Two Novel DNAAF2 Variants in Two Consanguineous Families with Primary Ciliary Dyskinesia
title_full	Identification of Two Novel DNAAF2 Variants in Two Consanguineous Families with Primary Ciliary Dyskinesia
title_fullStr	Identification of Two Novel DNAAF2 Variants in Two Consanguineous Families with Primary Ciliary Dyskinesia
title_full_unstemmed	Identification of Two Novel DNAAF2 Variants in Two Consanguineous Families with Primary Ciliary Dyskinesia
title_sort	identification of two novel dnaaf2 variants in two consanguineous families with primary ciliary dyskinesia
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/062f630993744098a407cf3c5011bebe
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Identification of Two Novel DNAAF2 Variants in Two Consanguineous Families with Primary Ciliary Dyskinesia

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