Corpus callosum abnormalities are common brain malformations with a wide clinical spectrum ranging from severe intellectual disability to normal cognitive function. The etiology is expected to be genetic in as much as 30–50% of the cases, but the underlying genetic cause remains unknown in the majority of cases. By next-generation mate-pair sequencing we mapped the chromosomal breakpoints of a patient with a de novo balanced translocation, t(1;6)(p31;q25), agenesis of corpus callosum (CC), intellectual disability, severe speech impairment, and autism. The chromosome 6 breakpoint truncated ARID1B which was also truncated in a recently published translocation patient with a similar phenotype. Quantitative polymerase chain reaction (Q-PCR) data showed that a primer set proximal to the translocation showed increased expression of ARID1B, whereas primer sets spanning or distal to the translocation showed decreased expression in the patient relative to a non-related control set. Phenotype–genotype comparison of the translocation patient to seven unpublished patients with various sized deletions encompassing ARID1B confirms that haploinsufficiency of ARID1B is associated with CC abnormalities, intellectual disability, severe speech impairment, and autism. Our findings emphasize that ARID1B is important in human brain development and function in general, and in the development of CC and in speech development in particular.

Our results strongly support the hypothesis that there is a molecular basis for phenotypic heterogeneity in phenylketonuria. The establishment of genotype will therefore aid in the prediction of biochemical and clinical phenotypes in patients with this disease.

Calcite crystals grown by organisms can be elaborate and enigmatic. One of the best examples is the tiny calcite shields known as coccoliths that are produced by unicellular algae. Coccoliths consist of interlocking single crystals of highly modiÞ ed morphology, and complex organic molecules called CAPs (coccolith associated polysaccharides) are known to be intimately associated with their formation. Here, we show how a CAP can regulate crystal morphology to enhance precipitation of speciÞ c faces, a crucial aspect of the biomineralization process.Using atomic force microscopy (AFM), we investigated the interaction of CAP from the species Emiliania huxleyi with the calcite surface during dissolution, precipitation, and dynamic equilibrium. We were able to see the polysaccharide adsorbed to the surface and observe its impact on mineral behavior. These experiments demonstrate that CAP preferentially interacts with surface sites deÞ ned by acute, rather than obtuse, angles and blocks acute sites during dissolution and growth. Therefore, CAP makes the calcite face that is most stable in the pure system, {101-4}, extend preferentially on the obtuse edges, promoting development of faces with lower angles to c-axis. AFM images of E. huxleyi at micrometer and atomic scales established that this is precisely the type of faces that deÞ ne the morphology of the coccolith crystals. Therefore, we propose that crystal shape regulation by CAP is a fundamental aspect of coccolith biomineralization, and that preferential growth inhibition by sitespeciÞ c functional groups is the mechanism causing CAP functionality.

Our findings suggest that non-syndromic PRS may be caused by both SOX9 and KCNJ2 dysregulation.