Mineralized polymeric biomaterials provide useful options toward mechanically robust systems for some tissue repairs. Silks as a mechanically robust protein-based material provide a starting point for biomaterial options, particularly when combined with silica toward organic− inorganic hybrid systems. To further understand the interplay between silk proteins and silica related to material properties, we systematically study the role of three key domains in bioengineered spider silk fusion proteins with respect to βsheet formation and mineralization: (i) a core silk domain for materials assembly, (ii) a histidine tag for purification, and (iii) a silicification domain for mineralization. Computational simulations are used to identify the effect of each domain on the protein folding and accessibility of positively charged amino acids for silicification and predictions are then compared with experimental data. The results show that the addition of the silica and histidine domains reduces β-sheet structure in the materials, and increases solvent-accessible surface area to the positive charged amino acids, leading to higher levels of silica precipitation. Moreover, the simulations show that the location of the charged biomineralization domain has small effect on the protein folding and consequently surface exposure of charged amino acids. Those surfaces display correlation with the amount of silicification in experiments. The results demonstrate that the exposure of the positively charged amino acids impacts protein function related to mineralization. In addition, processing parameters (solvating agent, the method of β-sheet induction and temperature) affect protein secondary structure, folding and function. This integrated modeling and experimental approach provides insight into sequence−structure−function relationships for control of mineralized protein biomaterial structures.

We aim to assess if genotype–phenotype correlations are present within ocular manifestations of Kabuki syndrome (KS) among a large multicenter cohort. We conducted a retrospective, medical record review including clinical history and comprehensive ophthalmological examinations of a total of 47 individuals with molecularly confirmed KS and ocular manifestations at Boston Children's Hospital and Cincinnati Children's Hospital Medical Center. We assessed information regarding ocular structural, functional, and adnexal elements as well as pertinent associated phenotypic features associated with KS. For both type 1 KS (KS1) and type 2 KS (KS2), we observed more severe eye pathology in nonsense variants towards the C‐terminus of each gene, KMT2D and KDM6A, respectively. Furthermore, frameshift variants appeared to be not associated with structural ocular elements. Between both types of KS, ocular structural elements were more frequently identified in KS1 compared with KS2, which only involved the optic disc in our cohort. These results reinforce the need for a comprehensive ophthalmologic exam upon diagnosis of KS and regular follow‐up exams. The specific genotype may allow risk stratification of the severity of the ophthalmologic manifestation. However, additional studies involving larger cohorts are needed to replicate our observations and conduct powered analyses to more formally risk‐stratify based on genotype, highlighting the importance of multicenter collaborations in rare disease research.

We report a patient with phenotypic semblance to the congenital microgastria-limb reduction association (MLRD). Our patient presented with microgastria, bilateral upper limb anomalies, asplenia, solitary kidney, and mild micrognathia. In addition to the anomalies seen in our patient, MLRD has been associated with respiratory, cardiovascular, and central nervous system anomalies. MLRD is thought to arise from a developmental field defect during embryonic weeks five and six; however, no genetic cause has been elucidated. Along with our patient presentation, we review the literature to further our understanding of the MLRD phenotype spectrum.