Loss-of-Function Variants in EFEMP1 Cause a Recognizable Connective Tissue Disorder Characterized by Cutis Laxa and Multiple Herniations

Maxim Verlee; Aude Beyens; Alper Gezdirici; Elif Yilmaz Gulec; Lore Pottie; Silke De Feyter; Michiel Vanhooydonck; Piyanoot Tapaneeyaphan; Sofie Symoens; Bert Callewaert

doi:10.3390/genes12040510

Loss-of-Function Variants in EFEMP1 Cause a Recognizable Connective Tissue Disorder Characterized by Cutis Laxa and Multiple Herniations

Genes (Basel). 2021 Mar 31;12(4):510. doi: 10.3390/genes12040510.

Authors

Maxim Verlee^{1

2}, Aude Beyens^{1

2

3}, Alper Gezdirici⁴, Elif Yilmaz Gulec⁵, Lore Pottie^{1

2}, Silke De Feyter^{1

2}, Michiel Vanhooydonck^{1

2}, Piyanoot Tapaneeyaphan^{1

2}, Sofie Symoens^{1

2}, Bert Callewaert^{1

2}

Affiliations

¹ Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium.
² Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium.
³ Department of Dermatology, Ghent University Hospital, 9000 Ghent, Belgium.
⁴ Department of Medical Genetics, Basaksehir Cam and Sakura City Hospital, 34480 Istanbul, Turkey.
⁵ Department of Medical Genetics, Kanuni Sultan Suleyman Training and Research Hospital, Health Sciences University, 34303 Istanbul, Turkey.

Abstract

Hereditary disorders of connective tissue (HDCT) compromise a heterogeneous group of diseases caused by pathogenic variants in genes encoding different components of the extracellular matrix and characterized by pleiotropic manifestations, mainly affecting the cutaneous, cardiovascular, and musculoskeletal systems. We report the case of a 9-year-old boy with a discernible connective tissue disorder characterized by cutis laxa (CL) and multiple herniations and caused by biallelic loss-of-function variants in EFEMP1. Hence, we identified EFEMP1 as a novel disease-causing gene in the CL spectrum, differentiating it from other HDCT.

Keywords: EFEMP1; FBLN3; cutis laxa; diaphragmatic hernia; elastic fiber; extracellular matrix; fibulin-3; inguinal hernia.

Publication types

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

MeSH terms

Child
Consanguinity
Cutis Laxa / genetics*
Diagnosis, Differential
Exome Sequencing
Extracellular Matrix Proteins / genetics*
High-Throughput Nucleotide Sequencing
Humans
Loss of Function Mutation*
Male
Pedigree

Substances

EFEMP1 protein, human
Extracellular Matrix Proteins