ABSTRACT
Approximately 50% of childhood deafness is caused by mutations in specific genes. Autosomal recessive loci account for approximately 80% of nonsyndromic genetic deafness. Here we report the identification of a new transmembrane serine protease (TMPRSS3; also known as ECHOS1) expressed in many tissues, including fetal cochlea, which is mutated in the families used to describe both the DFNB10 and DFNB8 loci. An 8-bp deletion and insertion of 18 monomeric (approximately 68-bp) beta-satellite repeat units, normally present in tandem arrays of up to several hundred kilobases on the short arms of acrocentric chromosomes, causes congenital deafness (DFNB10). A mutation in a splice-acceptor site, resulting in a 4-bp insertion in the mRNA and a frameshift, was detected in childhood onset deafness (DFNB8). This is the first description of beta-satellite insertion into an active gene resulting in a pathogenic state, and the first description of a protease involved in hearing loss.
Subject(s)
DNA, Satellite/genetics , Deafness/congenital , Deafness/enzymology , Genes, Recessive/genetics , Membrane Proteins , Mutagenesis, Insertional/genetics , Neoplasm Proteins , Serine Endopeptidases/genetics , Adult , Age of Onset , Base Sequence , Child , Consanguinity , Contig Mapping , DNA Mutational Analysis , Deafness/epidemiology , Deafness/genetics , Exons/genetics , Female , Frameshift Mutation/genetics , Humans , In Situ Hybridization, Fluorescence , Israel , Male , Molecular Sequence Data , Pakistan , Pedigree , RNA Splice Sites/genetics , RNA, Messenger/analysis , RNA, Messenger/genetics , Sequence Alignment , Serine Endopeptidases/metabolismABSTRACT
We report the first case of Lemierre's disease caused by a co-infection with A. haemolyticum and F. necrophorum. A characteristic skin rash and predominant growth on multiple blood cultures suggests a causative role for Arcanobacterium. Failures of penicillin therapy in A. haemolyticum infections should be considered when the initial antibiotic regimen is chosen.
Subject(s)
Actinomycetales Infections/complications , Actinomycetales/physiology , Fusobacterium Infections/complications , Jugular Veins/microbiology , Thrombophlebitis/complications , Thrombophlebitis/microbiology , Actinomycetales Infections/drug therapy , Adult , Anti-Bacterial Agents/therapeutic use , Drug Therapy, Combination/therapeutic use , Fusobacterium Infections/drug therapy , Humans , Jugular Veins/pathology , Male , Penicillanic Acid/analogs & derivatives , Penicillanic Acid/therapeutic use , Piperacillin/therapeutic use , Piperacillin, Tazobactam Drug Combination , Sepsis/complications , Sepsis/drug therapy , Sepsis/microbiology , Thrombophlebitis/drug therapy , Thrombophlebitis/etiology , Vancomycin/therapeutic useSubject(s)
Brain Diseases/diagnosis , Sarcoidosis/diagnosis , Syncope/etiology , Adult , Anti-Inflammatory Agents/therapeutic use , Brain Diseases/complications , Brain Diseases/drug therapy , Diagnosis, Differential , Female , Humans , Prednisone/therapeutic use , Sarcoidosis/complications , Sarcoidosis/drug therapyABSTRACT
Spinal epidural abscess (SEA) due to Streptococcus pneumoniae is rare and has never been reported in an HIV-infected patient, despite the higher risk of invasive disease in this group. We describe here the first case of pneumococcal epidural abscess, presenting with fever and back pain in a 60-year-old man infected with HIV. Blood cultures were positive for S. pneumoniae and magnetic resonance imaging (MRI) confirmed the suspicion of diskitis and SEA at the L4-S1 level. The patient was successfully treated with iv ceftriaxone without surgical intervention. The clinical characteristics of this case are compared with existing literature on pneumococcal SEA.
Subject(s)
AIDS-Related Opportunistic Infections/microbiology , Ceftriaxone/therapeutic use , Cephalosporins/therapeutic use , Epidural Abscess/microbiology , Streptococcal Infections/microbiology , AIDS-Related Opportunistic Infections/drug therapy , Epidural Abscess/drug therapy , Humans , Male , Middle Aged , Streptococcal Infections/drug therapy , Streptococcus pneumoniae/isolation & purification , Treatment OutcomeABSTRACT
Autosomal recessive childhood-onset non-syndromic deafness is one of the most frequent forms of inherited hearing impairment. Recently five different chromosomal regions, 7q31, 11q13.5, 13q12, 14q and the pericentromeric region of chromosome 17, have been shown to harbour disease loci for this type of neurosensory deafness. We have studied a large family from Pakistan, containing several consanguineous marriages and segregating for a recessive non-syndromic childhood-onset deafness. Linkage analysis mapped the disease locus (DFNB8) on the distal long arm of chromosome 21, most likely between D21S212 and D21S1225 with the highest lod score of 7.31 at theta = 0.00 for D21S1575 on 21q22.3.
Subject(s)
Chromosome Mapping , Chromosomes, Human, Pair 21 , Deafness/genetics , Adolescent , Age of Onset , Child , Consanguinity , Female , Genes, Recessive , Humans , Lod Score , Male , Pakistan , PedigreeABSTRACT
A large Pakistani family with several consanguineous marriages is described, in which autosomal recessive retinitis pigmentosa is segregating. Linkage studies revealed close linkage between the disease locus and six loci on chromosome 1q (D1S158, F13B, D1S422, D1S412, D1S413, and D1S53) with maximum lod scores ranging from 0.988-4.657 at theta = 0.065-0.235. However, the analysis of individual nuclear families showed very close linkage without recombination in three branches and several recombinants and negative lod scores throughout in the fourth branch. These results strongly suggest that mutations of two different genes are responsible for the disease in the 'linked' and 'unlinked' branches. Parallel to the linkage heterogeneity, clear phenotypic differences have been observed among the 'linked' and 'unlinked' parts. Our findings demonstrate that in case of recessive disorders the possibility of non-allelic genetic heterogeneity should always be considered, even within the same kindred and in genetic isolates if a largely extended pedigree is analysed.