title: Diagnosis implications of the whole genome sequencing in a large Lebanese family with hyaline fibromatosis syndrome.
abstract: Hyaline fibromatosis syndrome (HFS) is a recently introduced alternative term for two disorders that were previously known as juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH). These two variants are secondary to mutations in the anthrax toxin receptor 2 gene (ANTXR2) located on chromosome 4q21. The main clinical features of both entities include papular and/or nodular skin lesions, gingival hyperplasia, joint contractures and osteolytic bone lesions that appear in the first few years of life, and the syndrome typically progresses with the appearance of new lesions.
  
  
  
  We describe five Lebanese patients from one family, aged between 28 and 58 years, and presenting with nodular and papular skin lesions, gingival hyperplasia, joint contractures and bone lesions. Because of the particular clinical features and the absence of a clinical diagnosis, Whole Genome Sequencing (WGS) was carried out on DNA samples from the proband and his parents.
  
  
  
  A mutation in ANTXR2 (p. Gly116Val) that yielded a diagnosis of HFS was noted.
  
  
  
  The main goal of this paper is to add to the knowledge related to the clinical and radiographic aspects of HFS in adulthood and to show the importance of Next-Generation Sequencing (NGS) techniques in resolving such puzzling cases.
authors.affiliation: Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon.
authors.forename: Zahraa
authors.initials: Z
authors.lastname: Haidar
authors.affiliation: Bioinformatics Division, Sidra Medical & Research Center, Doha, Qatar.
authors.forename: Ramzi
authors.initials: R
authors.lastname: Temanni
authors.affiliation: Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon.
authors.forename: Eliane
authors.identifier: 0000-0002-6257-6609
authors.initials: E
authors.lastname: Chouery
authors.affiliation: Bioinformatics Division, Sidra Medical & Research Center, Doha, Qatar.
authors.forename: Puthen
authors.initials: P
authors.lastname: Jithesh
authors.affiliation: Genomics Core Laboratory, Translational Medicine Division, Sidra Medical & Research Center, Doha, Qatar.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Bioinformatics Division, Sidra Medical & Research Center, Doha, Qatar.
authors.forename: Rashid
authors.initials: R
authors.lastname: Al-Ali
authors.affiliation: Genomics Core Laboratory, Translational Medicine Division, Sidra Medical & Research Center, Doha, Qatar.
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.affiliation: Research office, Sidra Medical & Research Center, Doha, Qatar.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.affiliation: Unité de Génétique Médicale, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon.
authors.forename: Nadine
authors.initials: N
authors.lastname: Jalkh
authors.affiliation: Department of Radiology, Hotel Dieu de France University hospital-Beirut, Beirut, Lebanon.
authors.forename: Soha
authors.initials: S
authors.lastname: Haddad
authors.affiliation: Department of General surgery, Dar Al Amal University Hospital-Baalbeck, Baalbeck, Lebanon.
authors.forename: Wassim
authors.initials: W
authors.lastname: Haidar
authors.affiliation: Laboratory of Genetic Medicine and Immunology, Weill Cornell Medicine-Qatar, Doha, Qatar.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Chouchane
authors.affiliation: Institut Jérôme Lejeune, 37, rue des Volontaires, Paris, 75015, France. andre.megarbane@yahoo.fr.
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D057770:Hyaline Fibromatosis Syndrome / Q000000981:diagnostic imaging* / Q000235:genetics; D007861:Lebanon; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D018000:Receptors, Peptide / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: C447150:ANTXR2 protein, human; D018000:Receptors, Peptide
keywords: Anthrax toxin receptor 2 gene; Hyaline fibromatosis syndrome; Infantile systemic hyalinosis; Juvenile hyaline fibromatosis; Whole genome sequencing