Malmgren H, Sundvall M, Dahl N, Gustavson K H, Annerén G, Wadelius C, Steén-Bondeson M L, Pettersson U
Beijer Laboratory, Department of Medical Genetics, Biomedical Center, Uppsala University, Sweden.
Am J Hum Genet. 1993 Jun;52(6):1046-52.
A four-generation Swedish family with a new type of X-linked mental retardation syndrome was recently reported by Gustavson et al. The complex syndrome includes microcephaly, severe mental retardation, optical atrophy with decreased vision or blindness, severe hearing defect, characteristic facial features, spasticity, seizures, and restricted joint motility. The patients die during infancy or early in childhood. Twenty-one family members, including two affected males, were available for study. Linkage analysis was conducted in the family by using 11 RFLP markers and 10 VNTR markers spread along the X chromosome. A hypervariable short tandem repeat of DXS294 at Xq26 showed a peak two-point lod score of 3.35 at zero recombination fraction. Calculations using the 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 hte disease loci of two other syndromes with overlapping clinical manifestations recently were shown by Turner et al. and Pettigrew et al. to be linked to markers at Xq26.
古斯塔夫森等人最近报道了一个患有新型X连锁智力迟钝综合征的四代瑞典家族。该复杂综合征包括小头畸形、严重智力迟钝、视力减退或失明伴视神经萎缩、严重听力缺陷、特征性面部特征、痉挛、癫痫发作以及关节活动受限。患者在婴儿期或儿童早期死亡。有21名家庭成员可供研究，包括两名患病男性。通过使用沿X染色体分布的11个RFLP标记和10个VNTR标记对该家族进行连锁分析。位于Xq26的DXS294的一个高变短串联重复序列在零重组率时显示两点连锁lod值峰值为3.35。使用相同标记进行计算显示，DXS294处的多点连锁lod值峰值为3.65。与着丝粒标记DXS424和端粒标记DXS297的交叉事件确定了基因定位的可能区域。值得注意的是，特纳等人和佩蒂格鲁等人最近表明，另外两种具有重叠临床表现的综合征的疾病位点与Xq26处的标记连锁。
