@article {1723, title = {Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways.}, journal = {J Med Genet}, volume = {48}, year = {2011}, month = {2011 Jun}, pages = {369-74}, abstract = {

BACKGROUND: Hearing is a complex trait, but until now only a few genes are known to contribute to variability of this process. In order to discover genes and pathways that underlie auditory function, a genome-wide association study was carried out within the International Consortium G-EAR.

METHODS: Meta-analysis of genome-wide association study{\textquoteright}s data from six isolated populations of European ancestry for an overall number of 3417 individuals.

RESULTS: Eight suggestive significant loci (p<10(-7)) were detected with a series of genes expressed within the inner ear such as: DCLK1, PTPRD, GRM8, CMIP. Additional biological candidates marked by a single nucleotide polymorphism (SNP) with a suggestive association (p<10(-6)) were identified, as well as loci encompassing {\textquoteright}gene desert regions{\textquoteright}-genes of unknown function or genes whose function has not be linked to hearing so far. Some of these new loci map to already known hereditary hearing loss loci whose genes still need to be identified. Data have also been used to construct a highly significant {\textquoteright}in silico{\textquoteright} pathway for hearing function characterised by a network of 49 genes, 34 of which are certainly expressed in the ear.

CONCLUSION: These results provide new insights into the molecular basis of hearing function and may suggest new targets for hearing impairment treatment and prevention.

}, keywords = {Adaptor Proteins, Signal Transducing, Animals, Auditory Threshold, Carrier Proteins, Databases, Genetic, Europe, European Continental Ancestry Group, Female, Founder Effect, Genetic Linkage, Genome-Wide Association Study, Hearing, Hearing Loss, Humans, Intracellular Signaling Peptides and Proteins, Male, Mice, Phenotype, Polymorphism, Single Nucleotide, Protein-Serine-Threonine Kinases, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Receptors, Metabotropic Glutamate}, issn = {1468-6244}, doi = {10.1136/jmg.2010.088310}, author = {Girotto, Giorgia and Pirastu, Nicola and Sorice, Rossella and Biino, Ginevra and Campbell, Harry and d{\textquoteright}Adamo, Adamo P and Hastie, Nicholas D and Nutile, Teresa and Polasek, Ozren and Portas, Laura and Rudan, Igor and Ulivi, Sheila and Zemunik, Tatijana and Wright, Alan F and Ciullo, Marina and Hayward, Caroline and Pirastu, Mario and Gasparini, Paolo} } @article {1720, title = {Horizontal gaze palsy and progressive scoliosis without ROBO3 mutations.}, journal = {Ophthalmic Genet}, volume = {32}, year = {2011}, month = {2011 Nov}, pages = {212-6}, abstract = {

BACKGROUND: To describe clinical and genetic observations in a patient with horizontal gaze palsy and progressive scoliosis (HGPPS) without identified mutations in the ROBO3 gene.

MATERIALS AND METHODS: Neurologic and orthopedic evaluation of the proband; sequencing all exons, exon-intron boundaries, and promoter region of ROBO3 in the proband and his mother. Array CGH was also carried out in the proband and his mother to evaluate possible chromosomal deletion(s) and/or duplication(s).

RESULTS: The proband had complete horizontal gaze restriction with full vertical gaze and small amplitude horizontal pendular nystagmus. He also had severe scoliosis and brainstem hypoplasia pathognomonic of HGPPS. However, complete sequencing of ROBO3 twice in both forward and reverse directions did not reveal any mutations. Array CGH investigation revealed no chromosomal abnormalities.

CONCLUSIONS: This patient had clinical and neuroimaging characteristics considered pathognomonic of HGPPS and yet did not have ROBO3 mutations. A clinical misdiagnosis is unlikely in the absence of facial weakness (typical of Moebius syndrome), deafness (typical of the HOXA1 spectrum), or mental retardation (typical of other central decussation abnormalities). It is perhaps more likely that a phenotype identical to HGPPS can be caused by abnormalities in ROBO3 splice variant expression, by mutations of a gene other than ROBO3, or by some environmental or epigenetic factor(s) inhibiting the action of ROBO3 or its protein product in the developing brainstem.

}, keywords = {Child, Humans, Kyphosis, Magnetic Resonance Imaging, Male, Mutation, Ocular Motility Disorders, Oculomotor Nerve Diseases, Pedigree, Receptors, Immunologic, Scoliosis}, issn = {1744-5094}, doi = {10.3109/13816810.2011.574186}, author = {Abu-Amero, Khaled K and Faletra, Flavio and Gasparini, Paolo and Parentin, Fulvio and Pensiero, Stefano and Alorainy, Ibrahim A and Hellani, Ali M and Catalano, Dario and Bosley, Thomas M} }