Loss of function of the E3 ubiquitin-protein ligase UBE3B causes Kaufman oculocerebrofacial syndrome
| العنوان: | Loss of function of the E3 ubiquitin-protein ligase UBE3B causes Kaufman oculocerebrofacial syndrome |
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| المؤلفون: | Valentina Fodale, Viviana Caputo, Chiara Leoni, Andrea Ciolfi, Daniela Melis, Marco Tartaglia, Giuseppe Zampino, Laura Mazzanti, Antonio Pizzuti, Maria Francesca Bedeschi, Elisabetta Flex |
| المساهمون: | Flex, Elisabetta, Ciolfi, Andrea, Caputo, Viviana, Fodale, Valentina, Leoni, Chiara, Melis, Daniela, Bedeschi, Maria Francesca, Mazzanti, Laura, Pizzuti, Antonio, Tartaglia, Marco, Zampino, Giuseppe |
| المصدر: | Journal of Medical Genetics |
| بيانات النشر: | BMJ Publishing Group, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Ubiquitin-Protein Ligase, Microcephaly, Optic disk, Telecanthus, TUMOR-SUPPRESSOR GENE, PHENOTYPE, Kaufman oculocerebrofacial syndrome, Congenital, Diagnosis, Developmental, Exome, Genome-wide, Molecular genetics, Eye Abnormalities, Child, Author Keywords:Clinical genetics, Molecular genetics KeyWords Plus:JUVENILE MYELOMONOCYTIC LEUKEMIA, DNA-SEQUENCING DATA, GERMLINE MUTATIONS, ANGELMAN SYNDROME, IDENTIFICATION, DELINEATION, DEFICIENCY, EXPRESSION, Genetics (clinical), Exome sequencing, Genetics, Sanger sequencing, Homozygote, Hypotonia, Pedigree, Limb Deformities, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, clinical genetics, diagnosis, developmental, molecular genetics, genome-wide, symbols, Female, New Disease Loci, medicine.symptom, Diagnosi, Human, Clinical genetic, Ubiquitin-Protein Ligases, Molecular Sequence Data, Limb Deformities, Congenital, Biology, symbols.namesake, Genetic, Intellectual Disability, medicine, Humans, Clinical genetics, Base Sequence, Facies, medicine.disease, Facie, Protein ubiquitination, Eye Abnormalitie, Mutation, Molecular genetic |
| الوصف: | BACKGROUND: Kaufman oculocerebrofacial syndrome (KOS) is a developmental disorder characterised by reduced growth, microcephaly, ocular anomalies (microcornea, strabismus, myopia, and pale optic disk), distinctive facial features (narrow palpebral fissures, telecanthus, sparse and laterally broad eyebrows, preauricular tags, and micrognathia), mental retardation, and generalised hypotonia. KOS is a rare, possibly underestimated condition, with fewer than 10 cases reported to date. Here we investigate the molecular cause underlying KOS. METHODS: An exome sequencing approach was used on a single affected individual of an Italian consanguineous family coupled with mutation scanning using Sanger sequencing on a second unrelated subject with clinical features fitting the disorder. RESULTS: Exome sequencing was able to identify homozygosity for a novel truncating mutation (c.556C>T, p.Arg186stop) in UBE3B, which encodes a widely expressed HECT (homologous to the E6-AP carboxyl terminus) domain E3 ubiquitin-protein ligase. Homozygosity for a different nonsense lesion affecting the gene (c.1166G>A, p.Trp389stop) was documented in the second affected subject, supporting the recessive mode of inheritance of the disorder. Mutation scanning of the entire UBE3B coding sequence on a selected cohort of subjects with features overlapping, in part, those recurring in KOS did not reveal disease-causing mutations, suggesting phenotypic homogeneity of UBE3B lesions. DISCUSSION: Our data provide evidence that KOS is caused by UBE3B loss of function, and further demonstrate the impact of misregulation of protein ubiquitination on development and growth. The available clinical records, including those referring to four UBE3B mutation-positive subjects recently described as belonging to a previously unreported entity, which fits KOS, document the clinical homogeneity of this disorder. |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| تدمد: | 1468-6244 0022-2593 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::80d301ee366c85b12605f6f6f4cad004Test http://europepmc.org/articles/PMC3717725Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....80d301ee366c85b12605f6f6f4cad004 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14686244 00222593 |
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