The older brother has partial hearing loss and did develop basic academic skills, has some language, and can do some reading. The younger brother is deaf and has not developed academic skills. The mother had similar facial features, but no neurological or cognitive problems. Both patients had minimal response to levodopa, pimozide, trihexyphenidyl, clonidine, baclofen, clonazepam, and tetrabenazine. Workup, including serum carnitine, acyl-carnitine profile, very-long-chain fatty acids, creatine phosphokinase, arylsufatase, ß-galactosidase, carbohydrate deficient transferrin, complete blood count, complete metabolic profile, liver function tests, uric acid, lactate, pyruvate, ammonia, alpha-fetoprotein, immunoglobulins, inborn error screen, acanthocyte smear, biotinidase, thyroid studies, vitamin B12, folate, copper, ceruloplasmin, creatine, guanidinoacetate, urine and serum amino acids, urine organic acids, cerebrospinal fluid studies (protein, glucose, cells, immunoglobulins, lactate, pyruvate, oligoclonal bands, myelin basic protein, neurotransmitter metabolites, tetrahydrobiopterin, and neopterin), and electrophysiologic studies, was unremarkable. MRI of the brain performed on the older brother revealed delayed myelination, atrophy in posterior occipital lobes, hypoplasia of the superior cerebellar vermis, and thinning of the corpus callosum (Fig. 1). Genetic workup, including subtelomeric fluorescence in situ hybridization and screening for MERRF, MELAS, NARP, and Leigh's mutations, was negative. Nonrandom X-inactivation in studies of maternal DNA suggested X-linked transmission. Exome sequencing was performed on the entire family. Exons were captured with the Nimblegen SeqCap EZ Human Exome Library and sequenced with 2 × 100 base-pair (bp) paired-end reads on an Illumina HiSeq2000 (Illumina, Inc., San Diego, CA). Sequence was aligned to Hg19 using the Burrows-Wheeler Aligner (0.5.9)13, and variants were called with the Genome Analysis Toolkit (v. 1.6). More than 97% of bases sequenced had a quality score >10 and variants with a quality score <10 were removed to avoid false positives. Variants that had an allele frequency of >1% in dbSNP, the 1000 Genomes Project, and ESP were filtered out, leaving 564 variants present in at least 1 of the 2 brothers. Assuming an autosomal-recessive or X-linked mode of inheritance, filtering for two shared variants in autosomes and one shared variant in X chromosome in the two affected brothers, both patients were found to have a 6-bp deletion of c.261_266delGCTTCT, in exon 3 of BCAP31 (NM_001139457.1 MIM 300398), and the mother and sister were found to be carriers (Fig. 2). The 6-bp deletion at Xq28 results in a BAP31 protein change of p.Leu87_Leu89delinsPhe (deletion of leucines 88 and 89 and leucine 87 changed to phenylalanine). Analysis with MutationTaster showed that the mutated leucine residues are highly conserved and the mutation would potentially impact multiple functional domains, including the TOPO domain of the protein. The impact of this mutation on the protein was clearly predicted to be deleterious in Provean, with a score of −16.7 (cut-off score for deleterious change: −2.5). The deletion was confirmed by Sanger sequencing and is not in the Exome Aggregation Consortium (ExAC) database.