Notably, all mutations, which are not predicted to cause a loss of function, are clustered in two regions in the first half of the gene, exons 8–12 and exons 21–28. The mutations in the latter region affect the secretory pathway sec39 domain of NBAS (Figure 2). Individual F2:II.1 carries a homozygous missense variant and individual F3:II.1 an in-frame deletion of one amino acid compound heterozygous with a missense mutation. All other affected individuals are compound heterozygotes for one out of seven different predicted loss-of-function mutations (three stop mutations, two frameshift, and two splice site mutations) plus a missense mutation or a deletion of a single amino acid. None of the NBAS missense mutations is present in >120,000 alleles from the Exome Aggregation Consortium (ExAC) Server (12/2014). Three of the loss-of-function mutations, c.686dup (p.Ser230Glnfs∗4), c.2827G>T (p.Glu943∗), and c.3010C>T (p.Arg1004∗), are listed in the heterozygous state 59×, 8×, and 1×, respectively (MAF < 0.04%). Although we have no indication for a shared haplotype for the c.3164T>C variant identified heterozygous in three families, the exome data suggests a common founder c.2708T>G mutation in German families 2 and 4.