8p23.2-pter microdeletions: Seven new cases narrowing the candidate region and review of the literature
| Autor: | Anna Paola Capra, Ilaria Catusi, Rachele Cantone, Angela Peron, Flaviana Elia, Enrico Grosso, Silvana Briuglia, Monica Saccani, Maria Garzo, Corrado Romano, Maria Paola Recalcati, Lidia Larizza, Francesca Forzano, Ornella Galesi, Chiara Baldo, Michela Malacarne, Maria Paola Canevini |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Behavioral phenotypes Microcephaly Developmental delay Autism Spectrum Disorder Developmental Disabilities QH426-470 Chromosomal microarray analysis (CMA) Epilepsy 0302 clinical medicine Intellectual disability Behavior disorder Cognitive impairment Child Genetics (clinical) Sequence Deletion Genetics Small deletions 8p23.2-pter microdeletion 8p23.3 ARGHEF10 Candidate region Critical microdeletion region (CR) DLGAP2 Adolescent Adult Child Preschool Chromosome Deletion Chromosomes Human Pair 8 Cognitive Dysfunction Female Humans Infant Intellectual Disability Phenotype CLN8 Autism spectrum disorder Speech delay Pair 8 medicine.symptom Human Article Chromosomes 03 medical and health sciences medicine Preschool business.industry medicine.disease 030104 developmental biology business 030217 neurology & neurosurgery |
| Zdroj: | Genes Volume 12 Issue 5 Genes, Vol 12, Iss 652, p 652 (2021) |
| Popis: | To date only five patients with 8p23.2-pter microdeletions manifesting a mild-to-moderate cognitive impairment and/or developmental delay, dysmorphisms and neurobehavioral issues were reported. The smallest microdeletion described by Wu in 2010 suggested a critical region (CR) of 2.1 Mb including several genes, out of which FBXO25, DLGAP2, CLN8, ARHGEF10 and MYOM2 are the main candidates. Here we present seven additional patients with 8p23.2-pter microdeletions, ranging from 71.79 kb to 4.55 Mb. The review of five previously reported and nine Decipher patients confirmed the association of the CR with a variable clinical phenotype characterized by intellectual disability/developmental delay, including language and speech delay and/or motor impairment, behavioral anomalies, autism spectrum disorder, dysmorphisms, microcephaly, fingers/toes anomalies and epilepsy. Genotype analysis allowed to narrow down the 8p23.3 candidate region which includes only DLGAP2, CLN8 and ARHGEF10 genes, accounting for the main signs of the broad clinical phenotype associated to 8p23.2-pter microdeletions. This region is more restricted compared to the previously proposed CR. Overall, our data favor the hypothesis that DLGAP2 is the actual strongest candidate for neurodevelopmental/behavioral phenotypes. Additional patients will be necessary to validate the pathogenic role of DLGAP2 and better define how the two contiguous genes, ARHGEF10 and CLN8, might contribute to the clinical phenotype. |
| Databáze: | OpenAIRE |
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