Current Research and Scholarly Interests
Cystic fibrosis (CF) is a serious genetic condition caused by two disease-causing changes (mutations) in the CFTR gene. Additional genes have been implicated in CF-like disease. The types of mutations that cause CF and CF-like disease in individuals with African, Native American, Asian, or Middle Eastern backgrounds are not well known. The Schrijver laboratory and collaborators seek to reduce the disparity in mutation detection between Caucasian individuals and those of other or mixed extraction by adequately determining the mutation composition and individual frequencies in previously understudied populations. Such improved diagnostics are expected to allow earlier diagnosis and therapeutic management and could affect prognosis. This is an important step towards correlation of mutations (or combinations of mutations) with the clinical severity of symptoms. The knowledge of genotype-phenotype correlations can affect results reporting, counseling, prognosis predictions, and therapeutic decisions. Finally, the results can be considered in the review, evaluation, and optimization of individual State newborn testing algorithms.
Sensorineural hearing loss
Tremendous progress has been made in our understanding of the molecular basis of hearing and hearing loss. Through recent advances, the fascinating biology of the auditory system and new molecular mechanisms of hearing impairment have begun to be unveiled. Changes in the diagnostic impact of genetic testing have occurred, as well as exciting developments in therapeutic options (such as cochlear implants). Molecular diagnosis, which is already a reality for several hearing-associated genes, will continue to increase in the near future, both in terms of the number of mutations tested and the spectrum of genes. Inherited hearing loss, however, is characterized by impressive genetic heterogeneity. An abundance of genes carry a large number of mutations, but specific mutations in a single gene may lead to syndromic or nonsyndromic hearing loss. The Schrijver laboratory studies the genetics of hearing loss, with a focus on the DFNB1 locus, which contains the GJB2 and GJB6 genes. It is estimated that 50-70% of prelingual hearing loss is caused by genetic changes. Nonsyndromic (isolated) sensorineural hearing loss accounts for more than 70% of all hereditary hearing loss and up to half of that appears related to DFNB1. The Schrijver laboratory has shown that the GJB6 deletions del(GJB6-D13S1830) and del(GJB6-D13S1854), located upstream of the GJB2 gene, specifically inhibit the expression of GJB2 in cis with the deletions. We investigate the non-coding cis-regulatory sequence(s) responsible for controlling GJB2 expression and perform further genotyping in order to elucidate the genetic etiology underlying non-syndromic sensorineural hearing loss, and study genotype-phenotype correlations.