Mutations in a gene called CIB2, which provides the genetic code for a protein that binds both calcium and integrin, is associated with deafness—both in a disorder called Usher syndrome and in deafness that does not result from a syndrome, said an international group of researchers from Pakistan and the United States, including Baylor College of Medicine.

Many of the families studied were from Pakistan or parts of the Middle East, said Dr. Suzanne Leal, professor of molecular and human genetics at BCM and director of its Center for Statistical Genetics. Leal and colleagues from BCM are co-authors of the report in the journal Nature Genetics.

Two copies of mutated allele

Mutations in CIB2 cause autosomal recessive nonsyndromic hearing impairment where hearing impaired individuals have two copies of a mutated allele. Within the Pakistani population there are many genes involved in nonsyndromic hearing impairment; many of them are very rare causes of deafness. No single hearing impairment gene contributes substantially to hearing impairment in the Pakistani population. However, compared to other genes, CIB2 is a more common cause of non-syndromic hearing impairment within Pakistan. The CIB2 gene is also responsible for hearing impairment in people from the Middle East, but its role in other populations is still unknown.

"This gene is also involved in Usher syndrome," said Leal. Usher syndrome is the most common condition that affects both hearing and vision worldwide. The major symptoms of Usher syndrome are hearing loss and an eye disorder called retinitis pigmentosa. Usher syndrome occurs when a person inherits two mutated genes—one from each parent.

Hair cells, photoreceptor cells

In studies in mice, researchers identified the CIB2 protein in part of the inner ear hair cells and in photoreceptor and pigmented epithelial cells in the eye. The mutations identified in the non-syndromic forms of hearing loss altered the effect that CIB2 had on calcium responses in the cell. In zebrafish and Drosophila melanogaster (fruit flies), CIB2 is important in the function of hair cells and photoreceptor cells found in the retina.

Other institutions that took part in this study include Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio; the Institute on Deafness and
Other Communication Disorders, Rockville, Maryland; University of Kentucky in Lexington; University of the Punjab, Lahore, Pakistan; University of Miami in Florida; University of North Carolina at Chapel Hill; Quaid-i-Azam University, Islamabad, Pakistan; Baluchistan University of Information Technology, Quetta, Pakistan; University of Baluchistan, Quetta, Pakistan; Allama Iqbal Medical College, Lahore, Pakistan; University of Lahore, Lahore, Pakistan; and Zakariya University, Multan, Pakistan.

Other BCM researchers involved include Kwanghyuk Lee and Paula B Andrade-Elizondo.

Funding for this work came from Center for Inherited Disease Research (CIDR) fully funded through a federal contract (N01-HG-65403) from the US National Institutes of Health (NIH) to Johns Hopkins University; Research to Prevent Blindness; the Higher Education Commission and the Ministry of Science and Technology in Islamabad, Pakistan); the International Center for Genetic Engineering and Biotechnology in Trieste, Italy; the Cincinnati Children’s Hospital Research Foundation; the National Science Foundation and the U.S. National Institute on Deafness and Other Communication Disorders.