Is Autosomal Recessive Silver-Russel Syndrome a Separate Entity or Is It Part of the 3-M Syndrome Spectrum?
Is Autosomal Recessive Silver-Russel Syndrome a Separate Entity or Is It Part of the 3-M Syndrome Spectrum?
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DOI：
10.1002/ajmg.a.34009
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发表时间：
2011-06-01
影响因子：
2
通讯作者：
Al-Gazali, Lihadh
中科院分区：
文献类型：
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作者：
Akawi, Nadia A.;Ali, Bassam R.;Al-Gazali, Lihadh
宫内生长迟缓（IUGR）是一种非特异性的发现，发生在约0.17%的所有活产。然而，IUGR也可以是许多公认的遗传综合征的重要特征，包括Silver-Russel综合征（SRS），三M综合征（3-M），Dubowitz综合征和Mulibrey侏儒症。由于常染色体隐性SRS的表型变异性，3-M综合征与常染色体隐性SRS的鉴别一直很困难。肢体长度不对称见于超过一半的常染色体隐性SRS患者，但不见于3-M综合征患者。SRS中不存在3-M综合征的特征性影像学表现。我们使用单核苷酸多态性（SNP）微阵列调查SRS的表型特征的原因，显示常染色体隐性遗传在三个近亲家庭，两个来自阿拉伯联合酋长国（UAE），一个来自约旦。绘制的区域包含CUL 7和OBSL 1，这些基因最近被证明会导致3-M综合征。随后，对CUL 7和OBSL 1基因的直接DNA测序揭示了这两个基因中的新型突变，包括OBSL 1中的两个突变[c.1119G>C（p.W373C）和c.681_682delinsTT（p.Q228X）]，以及CUL 7中的无义突变[c.203G>A（p.W68X）]。另外，在阿联酋的一个近亲家系中发现CUL 7 [c.649_654delAGCCGC（p.217_218delSR）]有一个6个核苷酸的缺失，具有典型的3-M特征。由于这些发现，我们质疑的身份，常染色体隐性SRS，并建议所有明显的隐性SRS家庭应进行测试，在CUL 7和OBSL 1的突变。(C)2011 Wiley-Liss，Inc.
Intrauterine growth retardation (IUGR) is a nonspecific finding that occurs in approximately 0.17% of all live-births. However, IUGR can also be a significant feature of many recognized genetic syndromes including Silver-Russel syndrome (SRS), Three M syndrome (3-M), Dubowitz syndrome, and Mulibrey nanism. Differentiation of 3-M syndrome from autosomal recessive SRS has been difficult because of the phenotypic variability of the latter. Limb length asymmetry is seen in over half of those with autosomal recessive SRS, but not in individuals with 3-M syndrome. Characteristic radiologic findings of 3-M syndrome are not present in SRS. We used single nucleotide polymorphism (SNP) microarrays to investigate the cause of phenotypic features of SRS that shows autosomal recessive inheritance in three consanguineous families, two from United Arab Emirates (UAE), and one from Jordan. The mapped regions contained CUL7 and OBSL1, the genes that have recently been shown to cause 3-M syndrome. Subsequently, direct DNA sequencing of CUL7 and OBSL1 genes revealed novel mutations in both genes including two mutations in OBSL1 [c.1119G>C (p.W373C) and c.681_682delinsTT (p.Q228X)], and a nonsense mutation in CUL7 [c.203G>A (p.W68X)]. In addition, a six nucleotide deletion in CUL7 [c.649_654delAGCCGC(p.217_218delSR)] was found in a consanguineous family from UAE that had the typical features of 3-M. As a result of these findings, we question the identity of the autosomal recessive SRS and suggest that all apparently recessive SRS families should be tested for mutations in CUL7 and OBSL1. (C) 2011 Wiley-Liss, Inc.