Molecular characterization and prospective isolation of human fetal cochlear hair cell progenitors.

Sensory hair cells located in the organ of Corti are essential for cochlear mechanosensation. Their loss is irreversible in humans resulting in permanent hearing loss. The development of therapeutic interventions for hearing loss requires fundamental knowledge about similarities and potential differences between animal models and human development as well as the establishment of human cell based-assays.

Single-cell analysis delineates a trajectory toward the human early otic lineage.

Efficient pluripotent stem cell guidance protocols for the production of human posterior cranial placodes such as the otic placode that gives rise to the inner ear do not exist. Here we use a systematic approach including defined monolayer culture, signaling modulation, and single-cell gene expression analysis to delineate a developmental trajectory for human otic lineage specification in vitro. We found that modulation of bone morphogenetic protein (BMP) and WNT signaling combined with FGF and retinoic acid treatments over the course of 18 days generates cell populations that develop chronological expression of marker genes of non-neural ectoderm, preplacodal ectoderm, and early otic lineage.

Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder.

Background: Auditory neuropathy spectrum disorder (ANSD) is a form of hearing loss in which auditory signal transmission from the inner ear to the auditory nerve and brain stem is distorted, giving rise to speech perception difficulties beyond that expected for the observed degree of hearing loss. For many cases of ANSD, the underlying molecular pathology and the site of lesion remain unclear. The X-linked form of the condition, AUNX1, has been mapped to Xq23-q27.

Inner ear hair cell-like cells from human embryonic stem cells.

In mammals, the permanence of many forms of hearing loss is the result of the inner ear's inability to replace lost sensory hair cells. Here, we apply a differentiation strategy to guide human embryonic stem cells (hESCs) into cells of the otic lineage using chemically defined attached-substrate conditions. The generation of human otic progenitor cells was dependent on fibroblast growth factor (FGF) signaling, and protracted culture led to the upregulation of markers indicative of differentiated inner ear sensory epithelia.

Rare variants in BMP2 and BMP4 found in otosclerosis patients reduce Smad signaling.

Hypothesis: Genetic variation in BMP2 and BMP4 found in otosclerosis patients result in altered Smad signaling.

Background: Otosclerosis is a common form of adult-onset conductive hearing loss resulting from abnormal bone remodeling of the bony labyrinth that surrounds the inner ear. Both genetic and environmental factors are implicated in the disease, yet very little is known about its pathogenesis.

COL1A1 association and otosclerosis: a meta-analysis.

Otosclerosis is a disease of abnormal bone remodeling in the human otic capsule that can lead to progressive hearing loss. Little of the underlying disease etiology has been elucidated thus far, although several studies have suggested that COL1A1 may play a role based on its importance in bone metabolism and other diseases like osteoporosis and osteogenesis imperfecta. Genetic association studies between COL1A1 and otosclerosis, however, have been contradictory.

The prevalence of mitochondrial mutations associated with aminoglycoside-induced sensorineural hearing loss in an NICU population.

Several mitochondrial DNA variants increase risk for developing sensorineural hearing loss following exposure to aminoglycoside antibiotics, a particular concern in the premature infant population, as many of these babies spend time in neonatal intensive care units and are treated with aminoglycosides. To determine the relative prevalence of five mitochondrial DNA variants in the 12S rRNA gene, MT-RNR1, we genotyped 703 neonatal intensive care unit patients and 1473 individuals from the general Iowa population. We found that the aggregate frequency of these variants (∼1.

Otosclerosis.

Otosclerosis is one of the more common forms of adult-onset hearing loss with a prevalence of 0.3-0.4% in Caucasians.

Genetic variants in RELN are associated with otosclerosis in a non-European population from Tunisia.

Otosclerosis is a common form of conductive hearing loss, caused by an abnormal bone remodelling in the otic capsule. Both environmental and genetic factors have been implicated in the etiology of this disease. A recent genome wide association study identified two regions associated with otosclerosis, one on chr7q22.

Genetic variants in the RELN gene are associated with otosclerosis in multiple European populations.

Otosclerosis is a common form of hearing loss characterized by abnormal bone remodeling in the otic capsule. It is considered a complex disease caused by both genetic and environmental factors. In a previous study, we identified a region on chr7q22.

The genetics of otosclerosis.

Otosclerosis is a common form of conductive hearing loss with a prevalence of 0.3-0.4% in white adults.

No evidence for association between the renin-angiotensin-aldosterone system and otosclerosis in a large Belgian-Dutch population.

Hypothesis/background: Otosclerosis is a frequent cause of hearing impairment in the Caucasian population and is characterized by abnormal bone remodeling of the otic capsule. Associations with several genes have been reported, and recently, an association between the renin-angiotensin-aldosterone system and otosclerosis has been suggested. Polymorphisms in 3 genes were investigated: angiotensinogen (AGT), angiotensin I-converting enzyme (ACE), and angiotensin II receptor, type 1.

A genome-wide analysis identifies genetic variants in the RELN gene associated with otosclerosis.

Otosclerosis is a common form of progressive hearing loss, characterized by abnormal bone remodeling in the otic capsule. The etiology of the disease is largely unknown, and both environmental and genetic factors have been implicated. To identify genetic factors involved in otosclerosis, we used a case-control discovery group to complete a genome-wide association (GWA) study with 555,000 single-nucleotide polymorphisms (SNPs), utilizing pooled DNA samples.

Gene expression analysis of human otosclerotic stapedial footplates.

Otosclerosis is a complex disease that results in a common form of conductive hearing loss due to impaired mobility of the stapes. Stapedial motion becomes compromised secondary to invasion of otosclerotic foci into the stapedio-vestibular joint. Although environmental factors and genetic causes have been implicated in this process, the pathogenesis of otosclerosis remains poorly understood.

Association of bone morphogenetic proteins with otosclerosis.

Unlabelled: We studied the role of polymorphisms in 13 candidate genes on the risk of otosclerosis in two large independent case-control sets. We found significant association in both populations with BMP2 and BMP4, implicating these two genes in the pathogenesis of this disease.

Introduction: Otosclerosis is a progressive disorder of the human temporal bone that leads to conductive hearing loss and in some cases sensorineural or mixed hearing loss.

The coding polymorphism T263I in TGF-beta1 is associated with otosclerosis in two independent populations.

Otosclerosis is a progressive hearing loss characterized by an abnormal bone homeostasis of the otic capsule that leads to stapes fixation. Although its etiology remains unknown, otosclerosis can be considered a complex disease. Transforming growth factor-beta 1 (TGF-beta1) was chosen for a case-control association study, because of several non-genetic indications of involvement in otosclerosis.