Shaheen et al. (2013) reported on the underlying gene defects affecting Meckel-Gruber syndrome (MKS) patients from 18 consanguineous Saudi families.  Individuals were diagnosed with MKS based on the presence of occipital encephalocele as well as any combination of liver fibrosis, cleft palate, dysplastic kidneys, polydactyly and early lethality.  DNA from both affected and healthy members was obtained and an autozygome guided mutation analysis of known MKS genes was carried out.  When this did not uncover any mutations in some families, an exome sequencing was performed.  Exomes were then searched for compound heterozygous mutations in known MKS genes.  Failing that, all detected variants were filtered for homozygous novel changes within the autozygome. This approach helped detect a novel homozygous mutation in the TMEM237 gene (c.869+1G>A) that abolished a consensus donor site in one of the families.  This mutation resulted in exon skipping which was confirmed by RT-PCR.  An in-frame deletion of >60 amino acids was predicted (p.Met227_Arg291del).