title: Distal acroosteolysis, poikiloderma and joint stiffness: a novel laminopathy?
abstract: LMNA encodes lamin A and lamin C, two major components of the nuclear lamina, and its pathogenic variants lead to a dozen distinct clinical entities collectively known as laminopathies. Most LMNA-related laminopathies are autosomal dominant but four are autosomal recessive; furthermore, some of the dominant variants have been associated with distinct phenotypes when inherited recessively, further complicating the ability to correlate genotype with phenotype. We report a consanguineous family in which the index presented with an apparently unique constellation of poikiloderma, joint motion restriction and distal acroosteolysis but lacks features of muscle weakness, lipodystrophy, or cardiac or craniofacial involvement. Molecular analysis revealed the presence of a novel homozygous LMNA missense variant (NM_170707.3:c.1774G>A; p.(Gly592Arg)) within an area of autozygome that is not shared by his unaffected siblings. The proposed causal link is further supported by in silico analysis of this variant. Our case suggests an expansion of LMNA allelic disorders to include distal acroosteolysis, poikiloderma and joint stiffness (DAPJ).
authors.affiliation: Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
authors.forename: Wafaa
authors.initials: W
authors.lastname: Sewairi
authors.affiliation: Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Assiri
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Nisha
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.|Department of Anatomy and Cell Biology, College of Medicine Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: Amal
authors.initials: A
authors.lastname: Alhashem
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Department of Anatomy and Cell Biology, College of Medicine Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: Fowzan S
authors.identifier: 0000-0003-4158-341X
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D030981:Acro-Osteolysis / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D003241:Consanguinity; D006801:Humans; D007592:Joint Diseases / Q000175:diagnosis / Q000235:genetics*; D034904:Lamin Type A / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D012868:Skin Abnormalities / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A