Autozygosity Mapping with Exome Sequence Data

Autozygosity mapping is a powerful method for the identification of recessively inherited disease genes using small inbred families. Typically, microarray SNP genotype data are first used to identify autozygous regions as extended runs of homozygous genotypes. Next, candidate disease loci are found by defining regions that are autozygous in all affected patients. Finally, the disease gene is identified by sequencing the genes within the candidate disease loci. However, with the advent of massively parallel sequencing, it is now possible to sample or to completely sequence an individual's genome, or, more commonly, exome. This opens up the possibility of concurrently defining autozygous regions and identifying possibly deleterious sequence variants, using data from a single sequencing experiment. Consequently, we have developed a set of computer programs that identify autozygous regions using exome sequence data. These programs derive their genotyping data either by the ab initio detection of all sequence variants or by the assessment of 0.53 million known polymorphic positions within each exome dataset. Using genotype data derived solely from exome sequence data, it was possible to identify the majority of autozygous regions found by microarray SNP genotype data.     

Acute endophthalmitis caused by<Emphasis Type="Italic"> Staphylococcus lugdunesis</Emphasis> after intravitreal bevacizumab (Avastin) injection

Purpose To report a case of culture-positive endophthalmitis after intravitreal injection of bevacizumab (Avastin) resulting in a devastating visual outcome. Method A retrospective case report of a 51-year-old diabetic women who presented with further decrease in her vision, redness, and mild pain in her eye 3 days after intravitreal injection of Avastin for macular edema due to a branch retinal vein occlusion. Results Clinical diagnosis of endophthalmitis was made and, after obtaining a vitreous tap, intravitreal antibiotics were administered. Because of worsening of the endophthalmitis, pars plana vitrectomy was undertaken followed by repeat intravitreal antibiotics injection. The patient’s ocular condition improved dramatically; however, her visual acuity did not improve. The cultures from vitreous taps revealed Staphylococcus lugdunesis. Conclusion Intravitreal injection of Avastin may be associated with a risk of S. lugdunesis-caused endophthalmitis which can have a devastating effect on the final visual outcome.     

Further delineation of METTL23‐associated intellectual disability

METTL23 belongs to a family of methyltransferase like proteins (METTL) that transfer methyl group to various substrates. Recently, pathogenic homozygous variants in METTL23 were identified in patients from three families who presented with intellectual disability (ID) and variable dysmorphic features. In this report, we present unpublished phenotypic data from the original family as well as six new subjects from four families who also presented with mild to moderate ID and dysmorphic features, and were found to harbor four previously unpublished homozygous or compound heterozygous variants in METTL23. Our report further supports the role of this gene in autosomal recessive ID and emphasizes the mild but consistent facial features.