Haploinsufficiency for ANKRD11-flanking genes makes the difference between KBG and 16q24.3 microdeletion syndromes: 12 new cases
| Autor: | Novara, Francesca, Rinaldi, Berardo, Sisodiya, Sanjay M, Coppola, Antonietta, Giglio, Sabrina, Stanzial, Franco, Benedicenti, Francesco, Donaldson, Alan, Andrieux, Joris, Stapleton, Rachel, Weber, Astrid, Reho, Paolo, Van Ravenswaaij-Arts, Conny, Kerstjens-Frederikse, Wilhelmina S, Vermeesch, Joris Robert, Devriendt, Koenraad, Bacino, Carlos A, Delahaye, Andrée, Maas, S. M., Iolascon, Achille, Zuffardi, Orsetta, COPPOLA, ANTONIETTA |
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| Přispěvatelé: | Novara, Francesca, Rinaldi, Berardo, Sisodiya, Sanjay M, Coppola, Antonietta, Giglio, Sabrina, Stanzial, Franco, Benedicenti, Francesco, Donaldson, Alan, Andrieux, Jori, Stapleton, Rachel, Weber, Astrid, Reho, Paolo, Van Ravenswaaij-Arts, Conny, Kerstjens-Frederikse, Wilhelmina S, Vermeesch, Joris Robert, Devriendt, Koenraad, Bacino, Carlos A, Delahaye, Andrée, Maas, S. M., Iolascon, Achille, Zuffardi, Orsetta, Clinical Cognitive Neuropsychiatry Research Program (CCNP), ANS - Complex Trait Genetics, Human Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
ANKRD11 GENE Male Transcription Factor PROTEIN Haploinsufficiency Bioinformatics Intellectual disability Child Genetics (clinical) Nuclear Protein Genetics Nuclear Proteins Microdeletion syndrome Cadherins Phenotype Autism spectrum disorder Medical genetics HEART Female medicine.symptom Chromosome Deletion Human Adult medicine.medical_specialty Adolescent Biology Short stature PATIENT Article Tooth Abnormalitie Diagnosis Differential 03 medical and health sciences Genetic Genetic linkage Intellectual Disability medicine COFACTOR Humans Abnormalities Multiple Bone Diseases Developmental Tooth Abnormalities MUTATIONS DELETION Facies Repressor Protein medicine.disease Facie Human genetics Repressor Proteins 030104 developmental biology Cadherin TRANSCRIPTION FACTOR GATA-1 ERYTHROPOIESIS Chromosomes Human Pair 16 Transcription Factors |
| Zdroj: | European Journal of Human Genetics, 25(6), 694-701. Nature Publishing Group European journal of human genetics, 25(6), 694-701. Nature Publishing Group European Journal of Human Genetics |
| ISSN: | 1018-4813 |
| Popis: | 16q24 deletion involving the ANKRD11 gene, ranging from 137 kb to 2 Mb, have been associated with a microdeletion syndrome characterized by variable cognitive impairment, autism spectrum disorder, facial dysmorphisms with dental anomalies, brain abnormalities essentially affecting the corpus callosum and short stature. On the other hand, patients carrying either deletions encompassing solely ANKRD11 or its loss-of-function variants were reported in association with the KBG syndrome, characterized by a very similar phenotype, including mild-to-moderate intellectual disability, short stature and macrodontia of upper incisors, with inter and intrafamilial variability. To assess whether the haploinsufficiency of ANKRD11-flanking genes, such as ZFPM1, CDH15 and ZNF778, contributed to either the severity of the neurological impairment or was associated with other clinical features, we collected 12 new cases with a 16q24.2q24.3 deletion (de novo in 11 cases), ranging from 343 kb to 2.3 Mb. In 11 of them, the deletion involved the ANKRD11 gene, whereas in 1 case only flanking genes upstream to it were deleted. By comparing the clinical and genetic features of our patients with those previously reported, we show that the severity of the neurological phenotype and the frequency of congenital heart defects characterize the deletions that, besides ANKRD11, contain ZFPM1, CDH15 and ZNF778 as well. Moreover, the presence of thrombocytopenia and astigmatism should be taken into account to distinguish between 16q24 microdeletion syndrome and KBG syndrome. The single patient not deleted for ANKRD11, whose phenotype is characterized by milder psychomotor delay, cardiac congenital malformation, thrombocytopenia and astigmatism, confirms all this data.European Journal of Human Genetics advance online publication, 19 April 2017; doi:10.1038/ejhg.2017.49. ispartof: European Journal of Human Genetics vol:25 issue:6 pages:694-701 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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