The Genetics of Sensory Defects Unit* at Institut Pasteur, a major pioneer in research into the genetics of deafness, has demonstrated that more than half the cases of hereditary deafness in children are due to mutations in a single gene, DFNB1. This Unit, directed by Christine PETIT, has also clinically characterised these forms of hereditary deafness. This work, published in The Lancet, opens up new possibilities for the molecular diagnosis of deafness, which should considerably improve genetic counselling for affected families. The frequent involvement of DFNB1 in hereditary deafness also makes this gene a primary target for research into possible treatments.
Deafness is the most frequent sensory defect, affecting more than one child in every thousand at birth and one in every five hundred before adulthood. It may be hereditary or have an environmental cause (e.g. infection, medicines and noise). Until now, the etiology of deafness have been difficult to identify. Since 1994, The Genetics of Sensory Defects Unit of Institut Pasteur has carried out pioneering research into the genetic causes of deafness, by localizating the principal gene responsible, DFNB1. Today, it is estimated that more than fifty genes are responsible for hereditary deafness in children. In most cases, these genes are transmitted by a mechanism described as autosomal recessive. This means that both parents hear normally but one or more of their children are deaf. Six of the genes involved have been isolated, three by the Unit of Christine PETIT. DFNB1, which encodes connexin 26, is confirmed to be of outstanding importance.
In 1997, this laboratory showed that mutations of DFNB1 are responsible for half the cases of recessive hereditary deafness in children (1). The most common mutation of this gene is, along with that of the cystic fibrosis gene, the most frequent pathogenic mutation in man.
The researchers of Institut Pasteur carried out a prospective study of 140 children from 104 families, clinically characterising the types of deafness associated with mutations in the DFNB1 gene. In particular, individuals with mutations of this gene were found to suffer from various degrees of deafness (mild, moderate, severe or profound) and in most cases, the condition did not progress (2).
This first clinical characterisation of a genetic form of deafness, its high frequency and the ease with which it is now possible to screen for mutations of the DFNB1 gene make it possible, for the first time, to consider molecular diagnosis of deafness. This should considerably improve the genetic counselling available to deaf people and their families. The answers to the most frequently asked questions (is deafness hereditary? what is the risk for any children I might have in the future and how severe is their deafness likely to be? and could hearing loss progress ?) may be provided in many cases by analysis of the DFNB1 gene.
This work, in addition to improving the clinical exploration of deafness in children, will be of great value in the search for an effective treatment, because there is currently no known treatment for neurosensory deafness. By showing that a single gene is responsible for a large proportion of cases of hereditary deafness, Christine PETIT's laboratory has identified a target for future research efforts.
(1) "Prelingual deafness : high prevalence of a 30delG mutation
in the connexin26 gene" : Human Molecular Genetics. 1997,
6, 2173-2177.
Françoise DENOYELLE*,¤ , (…), and Christine
PETIT*.
(2) "Clinical features of the prevalent form of chilhood deafness,
DFNB1, due to a connexin-26 gene defect : implications for genetic counselling".
Lancet, 17 avril 1999, Vol 353, 1298-1303
Françoise DENOYELLE*,¤, Sandrine MARLIN*, Dominique
WEIL*, Lucien MOATTI¤, Pierre CHAUVINµ, Eréa-Noël
GARABEDIAN¤, Christine PETIT*.
* Unité de Génétique des Déficits Sensoriels,
CNRS URA 1968, Institut Pasteur, Paris.
¤ Service ORL, Hôpital d'Enfants Armand-Trousseau, Paris.
µ Unité de Recherche en Epidémiologie et Sciences de
l'Information, INSERM U 444, Faculté de Médecine Saint-Antoine,
Paris.
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