ABSTRACT
INTRODUCTION: Recently, You, Hoover-Fong, and colleagues described a disease caused by a deficiency of the telomere maintenance 2 gene (TELO2) function. The clinical spectrum includes early-onset global delay, dysmorphic facial features, auditory disorder, and reduced vision. MATERIALS AND METHODS: We report two siblings, diagnosed with You-Hoover-Fong syndrome at the age of 28 and 14 months. Both were genetically studied to find the cause of their developmental delay and microcephaly. RESULTS: The identical compound heterozygous missense mutations in the TELO2gene were found in each. Ophthalmologically, both siblings were diagnosed with progressive congenital bilateral nuclear-lamellar cataracts. CONCLUSIONS: We report nuclear-lamellar cataracts in two siblings diagnosed with You-Hoover-Fong syndrome.
Subject(s)
Cataract/pathology , Developmental Disabilities/pathology , Intellectual Disability/pathology , Microcephaly/pathology , Mutation, Missense , Telomere Homeostasis , Telomere-Binding Proteins/deficiency , Cataract/etiology , Child, Preschool , Developmental Disabilities/complications , Developmental Disabilities/genetics , Female , Humans , Infant , Intellectual Disability/complications , Intellectual Disability/genetics , Male , Microcephaly/complications , Microcephaly/genetics , Siblings , Telomere-Binding Proteins/metabolismABSTRACT
The glycoprotein 130 (gp130) dependent family of cytokines comprises interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), cardiotrophin-like cytokine (CLC), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1) and oncostatin M (OSM). These cytokines share the membrane gp130 as a common signal transducer. Recently, it was demonstrated that IL-6 promotes, whereas LIF inhibits fetal lung branching. Thus, in this study, the effects on fetal lung morphogenesis of the other classical members of the gp130-type cytokines (IL-11, CLC, CNTF, CT-1 and OSM) were investigated. We also provide the first description of these cytokines and their common gp130 receptor protein expression patterns during rat lung development. Fetal rat lung explants were cultured in vitro with increasing concentrations of IL-11, CLC, CNTF, CT-1 and OSM. Treated lung explants were morphometrically analyzed and assessed for MAPK, PI3K/AKT and STAT3 signaling modifications. IL-11, which similarly to IL-6 acts through a gp130 homodimer receptor, significantly stimulated lung growth via p38 phosphorylation. On the other hand, CLC, CNTF, CT-1 and OSM, whose receptors are gp130 heterodimers, inhibited lung growth acting in different signal-transducing pathways. Thus, the present study demonstrated that although cytokines of the gp130 family share a common signal transducer, there are specific biological activities for each cytokine on lung development. Indeed, cytokine signaling through gp130 homodimers stimulate, whereas cytokine signaling through gp130 heterodimers inhibit lung branching.
