Functional characterization of biallelic RTTN variants identified in an infant with microcephaly, simplified gyral pattern, pontocerebellar hypoplasia, and seizures

Jennifer A. Wambach, Daniel J. Wegner, Ping Yang, Marwan Shinawi, Dustin Baldridge, Ewelina Betleja, Joshua S. Shimony, David Spencer, Brian P. Hackett, Marisa V. Andrews, Thomas Ferkol, Susan K. Dutcher, Moe R. Mahjoub, F. Sessions Cole

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Biallelic deleterious variants in RTTN, which encodes rotatin, are associated with primary microcephaly, polymicrogyria, seizures, intellectual disability, and primordial dwarfism in human infants. Methods and results: We performed exome sequencing of an infant with primary microcephaly, pontocerebellar hypoplasia, and intractable seizures and his healthy, unrelated parents. We cultured the infant’s fibroblasts to determine primary ciliary phenotype. Results: We identified biallelic variants in RTTN in the affected infant: a novel missense variant and a rare, intronic variant that results in aberrant transcript splicing. Cultured fibroblasts from the infant demonstrated reduced length and number of primary cilia. Conclusion: Biallelic variants in RTTN cause primary microcephaly in infants. Functional characterization of primary cilia length and number can be used to determine pathogenicity of RTTN variants.

Original languageEnglish
Pages (from-to)435-441
Number of pages7
JournalPediatric research
Volume84
Issue number3
DOIs
StatePublished - Sep 1 2018

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