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PDCD6IP, encoding a regulator of the ESCRT complex, is mutated in microcephaly.

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.

SUBMITTER: Khan A

PROVIDER: S-EPMC8061709 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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PDCD6IP, encoding a regulator of the ESCRT complex, is mutated in microcephaly.

Khan Amjad A Alaamery Manal M Massadeh Salam S Obaid Abdulrahman A Kashgari Amna A AA Walsh Christopher A CA Eyaid Wafaa W

Clinical genetics 20200517 1

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 (ESC ...[more]

PMID: 32286682

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