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PDCD6IP,encoding a regulator of the ESCRT complex,is mutated in microcephaly |
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| Authors: | Amjad Khan Manal Alaamery Salam Massadeh Abdulrahman Obaid Amna A. Kashgari Christopher A. Walsh Wafaa Eyaid |
| Affiliation: | 1. Developmental Medicine Department, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia;2. Genetics Division, Department of Pediatrics, King Abdullah International Medical Research Centre (KAIMRC), King Saud bin Abdulaziz University for Health Science, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (MNGHA), Riyadh, Saudi Arabia;3. King Abdullah Specialized Children's Hospital (KASCH), Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia;4. Division of Genetics and Genomics and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, Massachusetts Department of Pediatrics, Harvard Medical School, Boston, Massachusetts Department of Neurology, Harvard Medical School, Boston, Massachusetts |
| Abstract: | Primary microcephaly (PM) is a highly heterogeneous neurodevelopmental disorder with many contributing risk genes and loci identified to date. We report a consanguineous family with PM, intellectual disability and short stature. Using whole exome sequencing, we identified a homozygous frameshift variant in programmed cell death 6 interacting protein (PDCD6IP, c.154_158dup; p.Val54Profs*18). This gene, PDCD6IP, plays an important role in the endosomal sorting complexes required for transport (ESCRT) pathway in the abscission stage of cytokinesis and apoptosis, and is required for normal brain development in mice. The clinical features observed in our patient were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies. This study provides evidence that clinical manifestations of PDCD6IP mutations as seen in our patients with PM and ID may be a novel cause for neurodevelopmental disorders. |
| Keywords: | consanguineous family intellectual disability microcephaly PDCD6IP whole exome sequencing |