Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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The recessive mode of transmission accounts for approximately 75% of inherited non syndromic deafness cases. We have previously designed the conditions for linkage studies of this highly heterogeneous disorder [Guilford et al. (1994) Nature Genet. 6, 24-28]. Here, using a similar approach, we have studied the segregation of a gene responsible for congenital, profound and fully penetrant sensorineural deafness in a consanguineous family living in an isolated region of Lebanon. A maximum lod score of 8.03 (theta = 0.00) was detected with a new polymorphic marker, AFMa052yb5 (D2S2144). Observed recombinants and homozygosity mapping define a maximum interval of 2 cM for this gene, DFNB6, which lies between AFMb346ye5 (a new polymorphic marker) (D2S2303) and AFM254vc9 (D2S174) on chromosome 2p22-23.
Hum Mol Genet 1996 Jan
PMID:A gene responsible for a sensorineural nonsyndromic recessive deafness maps to chromosome 2p22-23. 878 54

The recessive mutation at the mouse spinner (sr) locus results in hearing loss and vestibular dysfunction due to neuroepithelial defects in the inner ear. Using a positional cloning strategy, we have identified the mutant locus responsible for this pathology. The affected gene (Tmie) lies within a 40 kb deletion in the original sr allele. In a newly identified allele, Tmie contains a nonsense mutation expected to truncate the C-terminal end of its product. The 153 amino acid protein encoded by the gene shows no similarity to other known proteins, and is predicted to contain a signal peptide and at least one transmembrane domain. Tmie transcripts were identified in several tissues, including the cochlea. Loss of function of Tmie results in postnatal alterations of sensory hair cells in the cochlea, including defects in stereocilia, the apical projections of hair cells that are important in mechanotransduction of sound. These morphological defects are associated with a profound failure to develop normal auditory function. Consistent with a conserved role for this gene in the cochlea, the genetic mapping data presented here support human TMIE as the gene affected at DFNB6, a non-syndromic hearing loss locus. The spinner mutant is thus a valuable model for insight into mechanisms of human deafness and development of sensory cell function.
Hum Mol Genet 2002 Aug 01
PMID:Mutation of the novel gene Tmie results in sensory cell defects in the inner ear of spinner, a mouse model of human hearing loss DFNB6. 1214 Jan 91

Autosomal recessive nonsyndromic hearing loss (DFNB) is relatively frequent in Pakistan, which is thought to be mainly due to relatively frequent consanguinity. DFNB genes vary widely in their kinds and functions making molecular diagnosis difficult. This study determined the genetic causes in five Pakistani DFNB families with prelingual onset. The familial genetic analysis identified four pathogenic or likely pathogenic homozygous mutations by whole exome sequencing: two splicing donor site mutations of c.787+1G>A in ESRRB (DFNB35) and c.637+1G>T in CABP2 (DFNB93) and two missense mutations of c.7814A>G (p.Asn2605Ser) in CDH23 (DFNB12) and c.242G>A (p.Arg81His) in TMIE (DFNB6). The ESRRB and TMIE mutations were novel, and the TMIE mutation was observed in two families. The two missense mutations were located at well conserved sites and in silico analysis predicted their pathogenicity. This study identified four homozygous mutations as the underlying cause of DFNB including two novel mutations. This study will be helpful for the exact molecular diagnosis and treatment of deafness patients.
Mol Biol Rep 2020 Dec
PMID:Homozygous mutations in Pakistani consanguineous families with prelingual nonsyndromic hearing loss. 3326 33