Expansion of the spectrum of TUBB4A-related disorders: a new phenotype associated with a novel mutation in the TUBB4A gene.

Mutations in the TUBB4A gene have been identified so far in two neurodegenerative disorders with extremely different clinical features and course: whispering dysphonia, also known as dystonia type 4 (DYT4), and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). We describe a patient with slowly progressive spastic paraparesis, segmental dystonia, intellectual disability, behavioral problems, and evidence of permanent, incomplete myelination associated with progressive cerebellar atrophy. Whole exome sequencing revealed a novel E410K de novo heterozygous mutation in the TUBB4A gene.

A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes.

RNA molecules transmit the information encoded in the genome and generally reflect its content. Adenosine-to-inosine (A-to-I) RNA editing by ADAR proteins converts a genomically encoded adenosine into inosine. It is known that most RNA editing in human takes place in the primate-specific Alu sequences, but the extent of this phenomenon and its effect on transcriptome diversity are not yet clear.

Microcephaly thin corpus callosum intellectual disability syndrome caused by mutated TAF2.

Background: The combination of microcephaly, pyramidal signs, abnormal corpus callosum, and intellectual disability presents a diagnostic challenge. We describe an autosomal recessive disorder characterized by microcephaly, pyramidal signs, thin corpus callosum, and intellectual disability.

Methods: We previously mapped the locus for this disorder to 8q23.

Biallelic SZT2 mutations cause infantile encephalopathy with epilepsy and dysmorphic corpus callosum.

Epileptic encephalopathies are genetically heterogeneous severe disorders in which epileptic activity contributes to neurological deterioration. We studied two unrelated children presenting with a distinctive early-onset epileptic encephalopathy characterized by refractory epilepsy and absent developmental milestones, as well as thick and short corpus callosum and persistent cavum septum pellucidum on brain MRI. Using whole-exome sequencing, we identified biallelic mutations in seizure threshold 2 (SZT2) in both affected children.