Two Italian Patients with ELOVL4-Related Neuro-Ichthyosis: Expanding the Genotypic and Phenotypic Spectrum and Ultrastructural Characterization

Genes

Andrea Diociaiuti¹  May El Hachem¹  Diego Martinelli²  Giovanna Zambruno³  AngeloGiuseppe Condorelli³  Elisa Pisaneschi⁴  Claudia Cesario⁴  Sabrina Rossi⁵  Marina Macchiaiolo⁶  Francesco Nicita⁷ 

[1] Dermatology Unit, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio 4, 00165 Rome, Italy;Division of Metabolism, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio 4, 00165 Rome, Italy;Genodermatosis Unit, Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio 4, 00165 Rome, Italy;Laboratory of Medical Genetics, Department of Laboratories, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio, 4, 00165 Rome, Italy;Pathology Unit, Department of Laboratories, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio, 4, 00165 Rome, Italy;Rare Diseases and Medical Genetics Unit, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio, 4, 00165 Rome, Italy;Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio, 4, 00165 Rome, Italy;

关键词: ELOVL4;    ichthyosis;    collodion baby;    dysmorphism;    epilepsy;    developmental delay;   

DOI  :  10.3390/genes12030343

来源: DOAJ

【 摘 要 】

Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) is a fatty acid elongase responsible for very long-chain fatty acid biosynthesis in the brain, retina, and skin. Heterozygous mutations in ELOVL4 gene cause Stargardt-like macular dystrophy and spinocerebellar ataxia type-34, while different homozygous mutations have been associated with ichthyosis, spastic quadriplegia, and mental retardation syndrome in three kindred. We report the first two Italian children affected with neuro-ichthyosis due to the previously undescribed ELOVL4 homozygous frameshift variant c.435dupT (p.Ile146TyrfsTer29), and compound heterozygous variants c.208C>T (p.Arg70Ter) and c.487T>C (p.Cys163Arg), respectively. Both patients were born with collodion membrane followed by development of diffuse mild hyperkeratosis and scaling, localized erythema, and palmoplantar keratoderma. One infant displayed mild facial dysmorphism. They suffered from failure to thrive, and severe gastro-esophageal reflux with pulmonary aspiration. The patients presented axial hypotonia, hypertonia of limbs, and absent head control with poor eye contact from infancy. Visual evoked potentials showed markedly increased latency and poor morphological definition, indicative of alteration of the retro-retinal visual pathways in both patients. Ultrastructural skin examination revealed abnormalities of lamellar bodies with altered release in the epidermal granular and horny layer intracellular spaces. Our findings contribute to expanding the phenotypic and genotypic features of ELOVL4-related neuro-ichthyosis.

【 授权许可】

Unknown