Effects of RTTN gene mutations and the need for complementary cDNA analysis for some transcripts: case report

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Abstract RTTN is a gene coding for Rotatin protein which has been localized at ciliary body and centriole of human fibroblasts. Its exact function in human is not well identified. However, it is thought to play important role in maintenance of normal structure of primary cilia and hence in left to right organ specification, axial rotation, development of notochord as well as early cellular division in mice. Overall 28 cases have been reported with homozygous pathogenic mutations of RTTN gene till 2019 to our knowledge. They presented with primary microcephaly, short stature, polymicrogyria with or without seizures (MPPS). These symptoms can be summarized in microcephaly, generalized growth delay, malformation of the developing cortex (MDC) and hence neurodevelopmental delay with or without seizures. Meanwhile all of these signs usually appear in late prenatal or even postnatal life which emphasizes the need for other diagnostic tools in case of detection of RTTN variables of unknown significance or in case of accidental detection of multiple transcripts by NGS in prenatal genetic testing. A case with prenatal diagnosis of two different RTTN gene transcripts in fetal WES analysis. One of the transcripts showed RTTN homozygous gene mutation while the other transcript was normal. This article presents the multidisciplinary approach followed in prenatal as well as postnatal period. It also highlights the importance of gene expression analysis in prenatal genetics.