More than keratitis, ichthyosis, and deafness: Multisystem effects of lethal GJB2 mutations
العنوان: | More than keratitis, ichthyosis, and deafness: Multisystem effects of lethal GJB2 mutations |
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المؤلفون: | Alexander Maley, Barbara Binder, Adam E. Bennett, Karina L. Vivar, Keith A. Choate, Yasushi Ogawa, Amy Theos, Robert Sidbury, Earl J. Glusac, Gabriele Richard, Evelyn Lilly, Mary K. Spraker, Smail Hadj-Rabia, Masashi Akiyama, Raffaella A. Morotti, Shali Zhang, Lucia Seminario-Vidal, Christopher G. Bunick, Leonard M. Milstone |
المصدر: | Journal of the American Academy of Dermatology. 80:617-625 |
بيانات النشر: | Elsevier BV, 2019. |
سنة النشر: | 2019 |
مصطلحات موضوعية: | Male, Models, Molecular, Pediatrics, medicine.medical_specialty, Genotype, Dermatology, Serious infection, Deafness, Poor weight gain, Connexins, Infant Death, Article, Congenital Abnormalities, Keratitis, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, otorhinolaryngologic diseases, Humans, Medicine, Genotyping, Molecular Structure, business.industry, Ichthyosis, Body Weight, Infant, Newborn, Infant, medicine.disease, humanities, Pathophysiology, Infant mortality, Failure to Thrive, Connexin 26, 030220 oncology & carcinogenesis, Mutation, Female, Respiratory Tract Fistula, business |
الوصف: | Background Infant death in keratitis-ichthyosis-deafness (KID) syndrome is recognized; its association with specific genotypes and pathophysiology is inadequately understood. Objective We sought to discover characteristics that account for poor outcomes in lethal KID syndrome. Methods We collected 4 new cases and 9 previously reported, genotyped cases of lethal KID syndrome. We performed new molecular modeling of the lethal mutants GJB2 p.A88V and GJB2 p.G45E. Results Infant death occurred in all patients with GJB2 p.G45E and p.A88V; it is unusual with other GJB2 mutations. Early death with those 2 "lethal" mutations is likely multifactorial: during life all had ≥1 serious infection; most had poor weight gain and severe respiratory difficulties; many had additional anatomic abnormalities. Structural modeling of GJB2 p.G45E identified no impact on the salt bridge previously predicted to account for abnormal central carbon dioxide sensing of GJB2 p.A88V. Limitations This clinical review was retrospective. Conclusion GJB2 p.G45E and p.A88V are the only KID syndrome mutations associated with uniform early lethality. Those electrophysiologically severe mutations in GJB2 reveal abnormalities in many organs in lethal KID syndrome. All patients with KID syndrome may have subtle abnormalities beyond the eyes, ears, and skin. Early genotyping of KID syndrome births will inform prognostic discussion. |
تدمد: | 0190-9622 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d23c8b91aedfc4e433290af35b8146a8 https://doi.org/10.1016/j.jaad.2018.09.042 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....d23c8b91aedfc4e433290af35b8146a8 |
قاعدة البيانات: | OpenAIRE |
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