Wakui Keiko, Toyoda Atsushi, Kubota Takeo, Hidaka Eiko, Ishikawa Masayo, Katsuyama Tsutomu, Sakaki Yoshiyuki, Hattori Masahira, Fukushima Yoshimitsu
Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
J Hum Genet. 2002;47(10):511-6. doi: 10.1007/s100380200076.
We report a familial case with a proximal interstitial deletion of chromosome 21q [del(21q)]. Although the mother in the family was phenotypically normal, her first child was affected with both sensorineural hearing loss and moderate mental retardation, and the second affected child had mild mental retardation but not sensorineural hearing loss. We determined breakpoints of the del(21q) in the mother and her two affected children by fluorescence in situ hybridization analysis using 45 DNA clones and the molecular analysis using 21 DNA markers. The proximal breakpoint of the del(21q) was located at a region between 0.33 Mb and 0.46 Mb distal to the centromere, and the distal breakpoint was at a region between 14.6 Mb and 14.9 Mb. The finding indicates that the three individuals had an approximate 14-Mb deletion within 21q11.2-q21.3. Molecular analysis showed that both affected children shared the same maternal haplotype of their del(21q), but a crossover was detected in the paternally inherited normal chromosome 21. These data suggest that unmasking of deleterious genes on the paternally derived chromosome 21 of the two children as a result of the deletion may affect the extent of their mental retardation and/or sensorineural hearing loss. Usher syndrome 1E may be a candidate disease locus related to the sensorineural hearing loss of the first child.
我们报告了一例21号染色体长臂近端间质性缺失[del(21q)]的家族性病例。尽管该家族中的母亲表型正常，但其第一个孩子患有感音神经性听力损失和中度智力发育迟缓，第二个患病孩子有轻度智力发育迟缓但无感音神经性听力损失。我们通过使用45个DNA克隆的荧光原位杂交分析以及使用21个DNA标记的分子分析，确定了母亲及其两个患病孩子中del(21q)的断点。del(21q)的近端断点位于着丝粒远端0.33 Mb至0.46 Mb之间的区域，远端断点位于14.6 Mb至14.9 Mb之间的区域。这一发现表明这三个人在21q11.2 - q21.3范围内有一个约14 Mb的缺失。分子分析显示，两个患病孩子共享其del(21q)相同的母本单倍型，但在父系遗传的正常21号染色体上检测到一次交叉。这些数据表明，两个孩子父系来源的21号染色体上有害基因因缺失而暴露，可能影响其智力发育迟缓的程度和/或感音神经性听力损失。Usher综合征1E可能是与第一个孩子的感音神经性听力损失相关的候选疾病位点。
