Bocian Ewa, Hélias-Rodzewicz Zofia, Suchenek Kamila, Obersztyn Ewa, Kutkowska-Kaźmierczak Anna, Stankiewicz Paweł, Kostyk Ewa, Mazurczak Tadeusz
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
Med Sci Monit. 2004 Apr;10(4):CR143-51.
The etiology of mental retardation (MR) is unexplained in at least 50% of cases. Recently it was shown that subtle telomeric rearrangements may be a common cause of idiopathic mental retardation (IMR).
MATERIAL/METHODS: We studied 84 families with IMR and unspecific clinical features suggesting chromosomal aberration, including 59 patients with moderate to severe MR and 24 with mild MR. One healthy father of three deceased, severely MR children was also included. Fluorescence in situ hybridization (FISH) using 41 subtelomeric probes (the Chromoprobe Multiprobe--T System) was performed in all patients.
Ten (11.9%) subtle chromosome rearrangements were identified. Nine (10.7%) were subtelomeric abnormalities. Seven were familial, with six of paternal origin. All but one were products of parental balanced reciprocal translocation or inversion. Retrospective G-banding analysis showed that six of the nine rearrangements could be seen or suspected at the 450-550 band levels. Subtelomeric abnormalities were recognized in six patients with severe/moderate (including the father of children with severe MR) and in three with mild MR.
Our results confirm previous findings on the importance of subtelomeric rearrangements in the etiology of MR. They also show the diagnostic utility of subtelomeric FISH in detecting subtle telomeric rearrangements in IMR cases. The high proportion of familial rearrangements emphasizes their importance for genetic counseling. FISH screening was more reliable and efficient in identifying subtle telomeric abnormalities than G-banding analysis. However, as many of the subtelomeric abnormalities could be detected in retrospect even at the 550 band level, high-resolution G-banding analysis should always precede subtelomere assay. This is important for a better estimation of the real frequency of cryptic subtelomeric abnormalities.
至少50%的智力迟钝（MR）病例病因不明。最近研究表明，细微的端粒重排可能是特发性智力迟钝（IMR）的常见病因。
材料/方法：我们研究了84个患有IMR且有提示染色体畸变的非特异性临床特征的家庭，其中包括59例中重度MR患者和24例轻度MR患者。还纳入了一位有三个已故重度MR子女的健康父亲。对所有患者进行了使用41种亚端粒探针（染色体探针多探针-T系统）的荧光原位杂交（FISH）。
共鉴定出10例（11.9%）细微染色体重排。9例（10.7%）为亚端粒异常。7例为家族性，其中6例源自父亲。除1例之外，其余均为亲代平衡相互易位或倒位的产物。回顾性G显带分析显示，9例重排中的6例在450-550条带水平可见或可疑。6例重度/中度患者（包括重度MR患儿的父亲）和3例轻度MR患者中发现了亚端粒异常。
我们的结果证实了先前关于亚端粒重排在MR病因中重要性的研究结果。它们还显示了亚端粒FISH在检测IMR病例细微端粒重排中的诊断效用。家族性重排的高比例强调了它们在遗传咨询中的重要性。FISH筛查在识别细微端粒异常方面比G显带分析更可靠、更有效。然而，由于即使在550条带水平回顾性检测时也能发现许多亚端粒异常，因此在进行亚端粒检测之前应始终先进行高分辨率G显带分析。这对于更好地估计隐匿性亚端粒异常的实际频率很重要。
