Journal of Clinical & Experimental Dermatology Research
Open Access

Gaining insights into FAM111B: A recently identified gene implicated in multisystemic fibrosis

17^th European Dermatology Congress

March 01-03, 2018 | Paris, France

Afolake Arowolo, Dirk Lang, Nonhlanhla Khumalo, Bongani Mayosi and Edward Sturrock

Hair and Skin Research Lab, South Africa
Division of Physiological Sciences, Department of Human Biology, South Africa
Hatter Institute for Cardiovascular Research in Africa, South Africa
Division of Chemical and Systems Biology, Department of Integrative and Biomedical Science
University of Cape Town, South Africa

Posters & Accepted Abstracts: J Clin Exp Dermatol Res

Abstract :

Mutations in the FAM111B gene are associated with hereditary fibrosing poikiloderma (HFP), a recently described multisystemic fibrotic disease. We identified three missense mutations (Tyr621Asp, Arg626Gly and Ser628Asn) that span four families of different ethnic origin. However, the physiological and pathological role of FAM111B and mutated forms respectively is yet to be understood. Thus, to provide insights into the molecular function of the gene product of FAM111B, we investigated the subcellular localization in cells expressing FAM 111B. Through bioinformatics studies, we identified putative nuclear localization signal (NLS) in the amino acid sequence of FAM111B. We then expressed enhanced green fluorescent fusion proteins of wild-type FAM111B (FAM111B WT), mutants derived from HFP patients and truncated constructs (FAM111B-M255 and A375, up- and downstream of putative NLS sequence, respectively) in HEK293 cells. The cellular expression and subcellular localization of FAM111B were determined by confocal microscopy and supported by western blot analysis of the subcellular fractions of cells expressing FAM111B. We observed a predominantly nuclear expression of FAM111B WT while a diffused (nuclear and cytoplasmic) pattern of expression was seen with FAM111B-A375 and patientderived mutants. These findings suggest that the predicted NLS signal sequence may be active and that the identified mutations resulted in the aberrant translocation of FAM111B to the cytoplasm, thus leading to the reported disease phenotype afolakearowolo@gmail.com