Hearing loss (deafness) is one of the most frequent hereditary illnesses, affecting one in every thousand newborns. When it is not possible to identify an obvious cause of deafness in children through medical history or physical examination, genetic studies are the diagnostic tests that offer the best results.
However, due to the heterogeneity of the illness and the limited capacity of conventional DNA sequencing for analyzing the hundreds of genes involved in hearing swiftly and accurately, the genetic diagnosis of deafness has posed a challenge.
Researchers at IMOMA, led by Marta Diñeiro, Juan Cadiñanos and Rubén Cabanillas, the bioinformatics company DREAMgenics and colleagues from the Central University Hospital of Asturias (HUCA) and other Spanish hospitals, have recently published a paper in the scientific journal "BMC Medical Genomics", describing a new molecular tool, designed to optimize the genetic diagnosis of hereditary deafness, benefitting both patients and their families.
Genes contain the genetic information passed down from parents to their children. Certain variations in genetic sequences (mutations) may increase the predisposition to suffering specific diseases or directly cause them.
A significant proportion (10-40%, depending on the population) of hereditary deafness cases are due to variations in the GJB2 and GJB6 genes, whilst the rest are caused by alterations in any of the hundreds of other genes related to the illness. With the help of next-generation DNA sequencing (NGS), it is possible to analyze all of these genes.
The gene panel developed by IMOMA, DREAMgenics and their colleagues is based on the exhaustive analysis of 199 genes clearly associated in scientific papers with syndromic and non-syndromic, mixed and sensorineural hearing loss.
The panel was used in a pioneering national study carried out on a population of 50 Spanish patients with seemingly congenital hearing loss not caused by variations in GJB2 or GJB6, in order to analyze the usefulness of the tool in the most difficult scenarios.
In this population, the panel of selected genes - with technical specifications such as sensitivity and specificity over 99% - was capable of detecting the genetic cause in almost half of the patients. This figure is much higher than the results obtained with conventional methods. If we add the cases attributable to GJB2 and GJB6 (genes included in the platform, but excluded from the studied population), this figure would reach 60% of diagnosed cases.
Apart from the high efficiency of the test, in 28% of the diagnosed cases the tool identified syndromes that had not been clinically recognized before carrying out genetic analysis.
This represents a proof of concept of how genomics is changing clinical practice, making predictive and preventive medicine a reality, improving the lives of patients and their families and rationalizing costs in the health system.
In short, in the age of Precision Medicine, it is imperative to try to identify the cause of hereditary deafness.
With this paper, innovators at IMOMA and their colleagues have shown that, using the correct methodology, next generation sequencing can be transferred to clinical practice to improve diagnosis, provide prognostic information, identify hidden syndromes, cut costs and improve the quality of life of both patients and their families.