A neuropathological study of novel RTTN gene mutations causing a familial microcephaly with simplified gyral pattern.

ABSTRACT

BACKGROUND: The RTTN gene encodes Rotatin, a large centrosomal protein involved in ciliary functions. RTTN mutations have been reported in seven families and are associated with two phenotypes polymicrogyria associated with seizures and primary microcephaly associated with primordial dwarfism. CASE A targeted exome sequencing of morbid genes causing cerebral malformations identified novel RTTN compound heterozygous mutations in a family where three pregnancies were terminated because a severe fetal microcephaly was diagnosed. An autopsy performed on the second sib showed moderate growth restriction and a microcephaly with simplified gyral pattern. The histopathological study discovered a malformed cortical plate. CONCLUSIONS: The present study confirms the involvement of RTTN gene mutations in microcephaly with simplified gyral pattern and describes the observed abnormal neuropathological findings.