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

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.

SUBMITTER: Wambach JA 

PROVIDER: S-EPMC6258334 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature