LINKAGE MAPPING OF A SEVERE X-LINKED MENTAL-RETARDATION SYNDROME

A four-generation Swedish family with a new type of X-linked mental re tardation syndrome was recently reported by Gustavson et al. The compl ex syndrome includes microcephaly, severe mental retardation, optical atrophy with decreased vision or blindness, severe hearing defect, cha racteristic facial features, spasticity, seizures, and restricted join t motility. The patients die during infancy or early in childhood. Twe nty-one family members, including two affected males, were available f or study. Linkage analysis was conducted in the family by using 11 RFL P markers and 10 VNTR markers spread along the X chromosome. A hyperva riable short tandem repeat of DXS294 at Xq26 showed a peak two-point l od score of 3.35 at zero recombination fraction. Calculations using th e same markers revealed a multipoint peak lod score of 3.65 at DXS294. Crossover events with the centromeric marker DXS424 and the telomeric marker DXS297 delimit a probable region for the gene localization. It is noteworthy that the disease loci of two other syndromes with overl apping clinical manifestations recently were shown by Turner et al. an d Pettigrew et al. to be linked to markers at Xq26.