Pontocerebellar hypoplasia type III (CLAM): Extended phenotype and novel molecular findings
Pontocerebellar hypoplasia type III (CLAM): Extended phenotype and novel molecular findings
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DOI：
10.1007/s00415-009-0094-0
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发表时间：
2009-03-01
影响因子：
6
通讯作者：
Ozkinay, Ferda
中科院分区：
文献类型：
--
作者：
Durmaz, Burak;Wollnik, Bernd;Ozkinay, Ferda
桥小脑发育不全是一组以小脑和脑干异常小为特征的异质性疾病。最近，一种罕见的，新的形式的PCH已被报道称为小脑萎缩与进行性小头畸形（CLAM）。在这里，我们报告了第二个家庭的CLAM额外的表型特征和新的分子研究结果。3岁的索引患者有严重的发育迟缓，并提出了身材矮小和小头畸形。她的头颅磁共振成像显示小脑、脑干和大脑发育不全，伴有胼胝体发育不全。脑干听觉诱发电位显示听力下降，视觉诱发电位证实视神经萎缩。她还出现癫痫发作，脑电图显示有两个后部癫痫灶。分子分析揭示了在最初连锁区域内的标记D7S802和D7S630之间的纯合单倍型，将关键区域从20 Mb缩小到7 Mb。对位于该区域的两个高度相关的候选基因CROT和SLC25A40进行测序，但未鉴定出致病突变。我们的病例提供了额外的临床特征，对先前描述的功能，这种新的实体，减少关键区域，现在将允许系统的定位克隆的努力，以确定致病基因。
Pontocerebellar hypoplasia (PCH) is a heterogeneous group of disorders characterized by abnormally small cerebellum and brainstem. Recently a rare, novel form of PCH has been reported called cerebellar atrophy with progressive microcephaly (CLAM). Here we report a second family of CLAM with additional phenotypic features and novel molecular findings. Three-year old index patient had severe developmental delay and presented with short stature and microcephaly. Her cranial magnetic resonance imaging revealed hypoplasia of the cerebellum, brainstem and cerebrum associated with hypoplasia of the corpus callosum. Brainstem auditory evoked potentials revealed hearing loss and visual evoked potentials confirmed the optic atrophy. She also had seizures with two posterior epileptic foci on electroencephalogram. Molecular analysis revealed a homozygous haplotype between the markers D7S802 and D7S630 within the originally linked region, narrowing the critical region from 20 Mb to 7 Mb. Two highly relevant candidate genes, CROT and SLC25A40 located in this region were sequenced, but no causative mutations identified. Our case provides additional clinical characteristics on the previously described features of this new entity, and reducing the critical region will now allow systematic positional cloning efforts to identify the causative gene.