Brain malformation with loss of normal FGFR3 expression in thanatophoric dysplasia type I
Brain malformation with loss of normal FGFR3 expression in thanatophoric dysplasia type I
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DOI：
10.1111/neup.12036
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发表时间：
2013-12-01
期刊：
影响因子：
2.3
通讯作者：
Fushiki, Shinji
中科院分区：
文献类型：
--
作者：
Itoh, Kyoko;Pooh, Ritsuko;Fushiki, Shinji
致死性发育不良是一种致命性的软骨发育不良侏儒症，其大脑皮层表现为一种独特而复杂的畸形。我们报告一例女性的死亡性发育不良I型(TD1)的FGFR3突变。在这个病例中，怀孕18周的胎儿超声检查导致了具有特征性骨骼特征的TD1的产前诊断。受试者在怀孕21周时死产，长骨明显缩短，胸部较小，股骨弯曲，但没有三叶草头骨。颞叶增大，高度卷曲，表现为宽回深沟，由局灶性多微回样浅沟和位于中间带和边缘带的异位神经母细胞巢组成。在颞叶和枕叶增厚的内侧中间带和室下带可见丰富的前体细胞，Nestin和Ki-67免疫反应阳性，可见散在的核分裂。从内嗅皮层到阿蒙角的细胞结构紊乱，软脑膜神经胶质细胞异位，双重皮质素和巢蛋白免疫反应阳性。FGFR3在颞叶、枕叶或海马区几乎未见表达。基因分析发现FGFR3基因第7外显子C8526T(R248C)存在点突变。这是第一个表明在人类TD1病例中，FGFR3突变可能导致中间祖细胞过度生产的报告。
Thanatophoric dysplasia is a lethal form of chondrodysplastic dwarfism in which the cerebral cortex displays a unique and complex malformation. We report a female case of thanatophoric dysplasia type I (TD1) with FGFR3 mutation. In this case, fetal ultrasonography at the 18th week of gestation led to a prenatal diagnosis of TD1 with characteristic bone features. The subject was stillborn at the 21st week of gestation, showing marked shortening of the long bones, small thorax and curved short femurs, but without a cloverleaf skull. The temporal lobe was enlarged and hyperconvoluted, appearing as broad gyri and deep sulci, which were composed of focal polymicrogyria-like shallow sulci and heterotopic neuroblastic nests in the intermediate zone and marginal zone. Abundant precursor cells, immunoreactive for nestin and Ki-67 were observed with scattered mitoses in the thickened inner intermediate and subventricular zones of the temporal and occipital lobes. The cytoarchitecture from the entorhinal cortex to Ammon's horn was disorganized with leptomeningeal glioneuronal heterotopia, immunoreactive for doublecortin and nestin. The expression of FGFR3 was virtually not discernible in the temporal and occipital lobes or in the hippocampus. Genetic analysis revealed a point mutation at C8526T (R248C) in the exon 7 of FGFR3. This is the first report that demonstrates that overproduction of intermediate progenitor cells might be induced by FGFR3 mutation in a human TD1 case.