Whole-exome sequencing facilitates the differential diagnosis of Ehlers-Danlos syndrome (EDS)

Fang Yang; Rong-Juan Yang; Qian Li; Jing Zhang; Yan-Xin Meng; Xiao-Jun Liu; Yong-Feng Yao

doi:10.1002/mgg3.1885

Whole-exome sequencing facilitates the differential diagnosis of Ehlers-Danlos syndrome (EDS)

Mol Genet Genomic Med. 2022 Mar;10(3):e1885. doi: 10.1002/mgg3.1885. Epub 2022 Feb 4.

Authors

Fang Yang^{1

2}, Rong-Juan Yang³, Qian Li⁴, Jing Zhang⁵, Yan-Xin Meng⁵, Xiao-Jun Liu⁶, Yong-Feng Yao^{1

2}

Affiliations

¹ Department of Dermatology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.
² Candidate Branch of National Clinical Research Center for Skin Diseases, Shenzhen, China.
³ Department of Obstetrics, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, China.
⁴ National Research Institute for Family Planning, Beijing, China.
⁵ Prenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, China.
⁶ Department of Intensive Care Unit, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.

Abstract

Ehlers-Danlos syndromes (EDSs) are a group of rare monogenic conditions with strong heterogeneity and can be caused by 20 genes associating with the essence of the extracellular matrix (ECM). This study enrolled three cases with various subtypes of EDS. Clinical evaluation and genetic testing with whole-exome sequencing (WES) were performed. The clinical manifestations of all three patients were thoroughly monitored; and three de novo diagnostic variants, namely COL5A1: NM_001278074.1: c.4609-2A>C, COL3A1: NM_000090.3: c.3554G>T(p.Gly1185Val), and COL1A1: NM_000088.3: c.545G>T(p.Gly182Val) were identified from them, respectively. The findings in this study expanded the mutation spectrum of EDS and strengthened the efficiency of WES in the differential diagnosis on disorders with overlapping phenotypes and various pathogenesis.

Keywords: COL1A1; COL3A1; COL5A1; Ehlers-Danlos syndrome; whole-exome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diagnosis, Differential
Ehlers-Danlos Syndrome* / diagnosis
Ehlers-Danlos Syndrome* / genetics
Ehlers-Danlos Syndrome* / pathology
Exome Sequencing
Humans
Mutation
Phenotype