Masoumeh Hosseini - Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Luciana Musante - Max-Planck-Institute for Molecular Genetics, Berlin, Germany
Zohreh Fattahi - Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
Hao Hu - Max-Planck-Institute for Molecular Genetics, Berlin, Germany

Joubert syndrome (JBTS) is a clinically and genetically heterogeneous disorder with autosomal recessive pattern of inheritance. The disorder is characterized by cerebellar hypoplasia, intellectual disability (ID), ataxia and oculomotor apraxia. Other clinical features include retinal degeneration,renal anomalies, hepatic fibrosis, and skeletal involvement. The hallmark of JBTS is a radiological pattern at magnetic imaging resonance (MRI) named molar tooth sign . In 2007 Baala et al. identified a new form of Joubert syndrome designated JBTS6 with causative mutation in TMEM67 gene. To now only 5 mutations in this gene has been detected responsible forJBTS6.Due to high heterogeneity of ID in Iran, our study launched to find more causative genes and theirmutations in Iranian families affected with autosomal recessive ID using whole exome sequencing(WES). One of these families has two affected with profound ID, seizure, strabismus and renal failure in one affected. On WES data a number of variants detected in this family and with respect to theclinical features, a novel variant in TMEM67 gene chose as candidate. Because of suspicion of JS, MRIwas performed and molar tooth sign was observed. The variant co-segregated in the family and was absent normal population.Underlying causes of ID remain unknown in many cases because of clinical and genetic heterogeneity; therefor exome sequencing is an effective and helpful technique in detection of de novo mutation in this type of disorders. This approach results in more precise genotype-phenotype correlation and clinical diagnosis.

Joubert syndrome, TMEM67 gene, whole exome sequencing, novel variant, Iran