Bi-allelic Loss of Human APC2, Encoding Adenomatous Polyposis Coli Protein 2, Leads to Lissencephaly, Subcortical Heterotopia, and Global Developmental Delay
| Autor: | Sangmoon Lee, Ehsan Ghayoor Karimiani, Lauren Brick, Mariya Kozenko, Ghayda Mirzaa, Rachel Schot, M. Chiara Manzini, Kiely N. James, Henry Houlden, Grazia M.S. Mancini, Umut Altunoglu, Yalda Jamshidi, Dillon Y. Chen, Mehran Beiraghi Toosi, William B. Dobyns, Valentina Stanley, Reza Maroofian, Dalia Abdin, Tugba Kalayci, Heba Morsy, Jennifer McEvoy-Venneri, Nataliya Di Donato, Maha S. Zaki, Joseph G. Gleeson |
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| Přispěvatelé: | Clinical Genetics |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Microcephaly band heterotopia Developmental Disabilities Intellectual and Developmental Disabilities (IDD) Lissencephaly Classical Lissencephalies and Subcortical Band Heterotopias Biology Medical and Health Sciences 03 medical and health sciences Epilepsy PAFAH1B1 0302 clinical medicine Microtubule Report Genetics medicine Humans pachygyria Global developmental delay Alleles Genetics (clinical) Genetics & Heredity agyria neuronal migration Pachygyria Neurosciences Biological Sciences medicine.disease Pedigree Brain Disorders Cytoskeletal Proteins 030104 developmental biology Heterotopia (medicine) intellectual disability Neurological APC2 epilepsy Female Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | American Journal of Human Genetics, 105(4), 844-853. Cell Press American journal of human genetics, vol 105, iss 4 |
| ISSN: | 0002-9297 1537-6605 |
| DOI: | 10.1016/j.ajhg.2019.08.013 |
| Popis: | Lissencephaly is a severe brain malformation in which failure of neuronal migration results in agyria or pachygyria and in which the brain surface appears unusually smooth. It is often associated with microcephaly, profound intellectual disability, epilepsy, and impaired motor abilities. Twenty-two genes are associated with lissencephaly, accounting for approximately 80% of disease. Here we report on 12individuals with a unique form of lissencephaly; these individuals come from eight unrelated families and have bi-allelic mutations in APC2, encoding adenomatous polyposis coli protein 2. Brain imaging studies demonstrate extensive posterior predominant lissencephaly, similar to PAFAH1B1-associated lissencephaly, as well as co-occurrence of subcortical heterotopia posterior to the caudate nuclei, "ribbon-like" heterotopia in the posterior frontal region, and dysplastic in-folding of the mesial occipital cortex. The established role of APC2 in integrating the actin and microtubule cytoskeletons to mediate cellular morphological changes suggests shared function with other lissencephaly-encoded cytoskeletal proteins such as α-N-catenin (CTNNA2) and platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1, also known as LIS1). Our findings identify APC2 as a radiographically distinguishable recessive form of lissencephaly. |
| Databáze: | OpenAIRE |
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