A NEW X-LINKED RECESSIVE DEAFNESS SYNDROME WITH BLINDNESS, DYSTONIA, FRACTURES, AND MENTAL DEFICIENCY IS LINKED TO XQ22

X linked recessive deafness accounts for only 1.7% of all childhood de afness. Only a few of the at least 28 different X linked syndromes ass ociated with hearing impairment have been characterised at the molecul ar level. In 1960, a large Norwegian family was reported with early on set progressive sensorineural deafness, which was indexed in McKusick as DFN-1, McKusick 304700. No associated symptoms were described at th at time. This family has been restudied clinically. Extensive neurolog ical, neurophysiological, neuroradiological, and biochemical, as well as molecular techniques, have been applied to characterise the X linke d recessive syndrome. The family history and extensive characterisatio n of 16 affected males in five generations confirmed the X linked rece ssive inheritance and the postlingual progressive nature of the sensor ineural deafness. Some obligate carrier females showed signs of minor neuropathy and mild hearing impairment. Restudy of the original DFN-1 family showed that the deafness is part of a progressive X linked rece ssive syndrome, which includes visual disability leading to cortical b lindness, dystonia, fractures, and mental deficiency. Linkage analysis indicated that the gene was Linked to locus DXS101 in Xq22 with a lod score of 5.37 (zero recombination). Based on lod-l support interval o f the multipoint analysis, the gene is located in a region spanning fr om 5 cM proximal to 3 cM distal to this locus. As the proteolipid prot ein gene (PLP) is within this region and mutations have been shown to be associated with non-classical PMD (Pelizaeus-Merzbacher disease), s uch as complex X linked hereditary spastic paraplegia, PLP may represe nt a candidate gene for this disorder. This family represents a new sy ndrome (Mohr-Tranebjaerg syndrome, MTS) and provides significant new i nformation about a new X Linked recessive syndromic type of deafness w hich was previously thought to be isolated deafness.