EXPANDED PHENOTYPE OF TMEM67 GENE MUTATION (CASE REPORT)

Human ciliopathies are a class of multi-organ genetic disorders caused by defects of proteins expressed at the primary cilium, an organelle present on the cell surface of almost all cell types. Thus far, dozens of causative genes for ciliopathies have been identified and many of them are known to cause allelic disease. Of particular interest is the TMEM67 gene, encoding the transmembrane protein meckelin. The involvement of the mutant TMEM67 gene is known to be associated with a broad range of clinical presentations, namely Joubert syndrome 6 (JBTS6), nephronophthisis 11 (NPHP11), Bardet-Biedel syndrome (BBS), COACH syndrome, and lethal Meckel syndrome type 3 (MKS3). Here we present a case of a 3-year-old boy with compound heterozygous missense mutations in the TMEM67 gene manifesting features of both JBTS and NPHP syndromes, with neonatal onset of end-stage renal disease (ESRD) and associated microcephaly. Such a phenotype has not been reported to date, thus highlighting the diversity of ciliopathies and expanding the phenotype of the TMEM67 gene.