The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains.

A major milestone of child development is the acquisition and use of speech and language. Communication disorders, including speech sound disorder (SSD), can impair a child's academic, social and behavioral development. Speech sound disorder is a complex, polygenic trait with a substantial genetic component. However, specific genes that contribute to SSD remain largely unknown. To identify associated genes, we assessed the association of the DYX2 dyslexia risk locus and markers in neurochemical signaling genes (e.g., nicotinic and dopaminergic) with SSD and related endophenotypes. We first performed separate primary associations in two independent samples - Cleveland SSD (210 affected and 257 unaffected individuals in 127 families) and Denver SSD (113 affected individuals and 106 unaffected individuals in 85 families) - and then combined results by meta-analysis. DYX2 markers, specifically those in the 3' untranslated region of DCDC2 (P = 1.43 × 10(-4) ), showed the strongest associations with phonological awareness. We also observed suggestive associations of dopaminergic-related genes ANKK1 (P = 1.02 × 10(-2) ) and DRD2 (P = 9.22 × 10(-3) ) and nicotinic-related genes CHRNA3 (P = 2.51 × 10(-3) ) and BDNF (P = 8.14 × 10(-3) ) with case-control status and articulation. Our results further implicate variation in putative regulatory regions in the DYX2 locus, particularly in DCDC2, influencing language and cognitive traits. The results also support previous studies implicating variation in dopaminergic and nicotinic neural signaling influencing human communication and cognitive development. Our findings expand the literature showing genetic factors (e.g., DYX2) contributing to multiple related, yet distinct neurocognitive domains (e.g., dyslexia, language impairment, and SSD). How these factors interactively yield different neurocognitive and language-related outcomes remains to be elucidated.

Genome-wide association study of shared components of reading disability and language impairment.

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.

Genetic influences of cortical gray matter in language-related regions in healthy controls and schizophrenia.

Individuals with schizophrenia show a broad range of language impairments, including reading difficulties. A recent structural MRI (sMRI) study linked these difficulties to structural abnormalities in language-related regions (Leonard et al., 2008). Similar regions have been implicated in primary reading disability (RD). Major hypotheses of RD implicate abnormal embryonic neuronal migration in the cortex, and genetic linkage and association studies have identified a number of candidate RD genes that are associated with neuronal migration (Paracchini et al., 2007). Interestingly, evidence suggests at least some individuals with schizophrenia also show impaired neuronal migration in the cortex (Akbarian et al., 1996). Thus the aim of this study was to examine the link between RD-related genes and gray matter volumes in healthy controls and schizophrenia. We used parallel independent component analysis (parallel-ICA) to examine the relationship between gray matter volumes extracted using voxel-based morphometry (VBM) and 16 single nucleotide polymorphisms (SNPs) spanning FOXP2 and four RD-related genes, DCDC2, DYX1C1, KIAA0319 and TTRAP. Parallel-ICA identified five sMRI-SNP relationships. Superior and inferior cerebellar networks were related to DYX1C1 and DCDC2/KIAA0319 respectively in both groups. The superior prefrontal, temporal and occipital networks were positively related to DCDC2 in the schizophrenia, but not the control group. The identified networks closely correspond to the known distribution of language processes in the cortex. Thus, reading and language difficulties in schizophrenia may be related to distributed cortical structural abnormalities associated with RD-related genes.

The reintroduction and possible establishment of Aedes albopictus in New Mexico.

We report on the collection of adults and larvae of Aedes albopictus from Carlsbad, New Mexico. In 1989, in Albuquerque, individual adults of this species were intercepted and destroyed. This recent investigation in Carlsbad disclosed the presence of adults from four sites and larvae from one site, on August 19 and on September 12, 14, and 15, 2005.

Myiasis in humans: an overview and a report of two cases in the Republic of Panama.

This paper on myiasis provides varied references from documented sources as an overall review. A review of two case studies, a primary screwworm (cochliomyia hominivorax) infestation and a human botfly (Dermatobia hominis) infestation, as well as information on approaches to positive intervention and remediation are presented. Human myiasis found in the subtropical and tropical regions of the world is a health threat. As a result of the military's expanding role in medical support to various regions where myiasis is endemic, this paper serves to familiarize health care providers with this condition and to provide guidance when dealing with patients affected by myiasis.

Myiasis in a wounded soldier returning from Panama.

An imported case of traumatic myiasis occurred in a soldier wounded during military action in Panama in December 1989 and evacuated to Brooke Army Medical Center, Fort Sam Houston, Texas. At the medical center, five larvae were removed from the scalp wound, reared to the adult stage, and identified as Cochliomyia hominivorax (Coquerel). Though this was the only reported case of wound myiasis of the 254 servicemen evacuated for medical treatment, this incident indicates a potential mechanism for the reintroduction of C. hominivorax into the United States.

Mutagenic potential of 4 organophosphinate compounds.

The mutation frequency of four organophosphinate compounds at various concentrations currently being investigated for their prophylactic ability in anticholinesterase poisoning was assessed using the sexlinked recessive lethal (SLRL) assay. Fisher's Exact Test indicated non-significant differences (P greater than 0.05) for: 4-nitrophenyl methyl (phenyl) phosphinate at 0.002 mM; 4-nitrophenyl monochloromethyl (phenyl) phosphinate at 0.007, 0.05 and 0.01 mM; 4-nitrophenyl diphenyl phosphinate at 0.35 and 0.51 mM; and 4-nitrophenyl dimethyl phosphinate at 0.005 and 0.01 mM compared to concurrent negative controls. This non-mutagenic activity of these four compounds was also confirmed by other researchers using the Ames assay.

Mutation frequencies of Drosophila melanogaster reared in glass and plastic vials.

The mutation frequency of the sex-linked recessive lethal assay resulting from the examination of 9032 tests of Drosophila melanogaster reared in plastic vials (0.198%) was approximately twice that of Drosophila melanogaster reared in glass vials (0.085%) after examination of 9365 tests. This difference was found to be significant (P less than 0.05). This significant increase in the mutation frequency may be due to styrene which is one of the components of the plastic vials. Also, the frequency of failure was greater when using plastic vials (1.19%) compared to glass vials (0.71%). In the following study we examined D. melanogaster SLRL mutation frequencies and failure rates when using glass and plastic vials. Our results showed a doubling in the SLRL mutation rate.