Boucher-Neuhauser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: two novel cases and a review of 40 cases from the literature
Boucher-Neuhauser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: two novel cases and a review of 40 cases from the literature
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DOI：
10.1007/s00415-014-7555-9
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发表时间：
2015-01-01
影响因子：
6
通讯作者：
Synofzik, M.
中科院分区：
文献类型：
--
作者：
Tarnutzer, A. A.;Gerth-Kahlert, C.;Synofzik, M.
进行性小脑变性、低促性腺激素性性腺功能减退症和脉络膜视网膜营养不良的结合定义了罕见的 Boucher-Neuhauser 综合征 (BNS)，最近发现该综合征与四名指标患者中 PNPLA6 基因的常染色体隐性突变有关。在这里，我们介绍了两名新的不相关的 BNS 患者，我们使用有针对性的高通量方法确定了四种隐性 PNPLA6 突变（其中 3 个是新突变）作为遗传原因。这一发现首次从独立家族中复制了 BNS 是由 PNPLA6 引起的，而且强调了 PNPLA6 是导致 BNS 的主要基因。鉴于现已确定导致 BNS 的主要基因，我们基于对先前发表的病例文献 (n = 40) 的系统深入回顾，总结了 BNS 的临床表现和表型进化谱。这里介绍的两个病例以及我们对文献的回顾都表明，BNS 的临床表现可能因年龄（1 至 40 岁）和发病时的临床症状而异（38% 为小脑性共济失调；36% 为视力丧失；26% 为青春期延迟）。相当一部分 BNS 病例可能会出现相对选择性的小脑蚓部上部和背侧萎缩，以及 MRI 上的小脑半球萎缩，而 MRI 上的脑干或皮质变化似乎只存在一小部分。此外，在文献中，除了 PNPLA6 突变之外，没有发现 BNS 的其他主要遗传原因。
The combination of progressive cerebellar degeneration, hypogonadotropic hypogonadism and chorioretinal dystrophy defines the rare Boucher-Neuhauser syndrome (BNS), which has recently been linked to autosomal-recessive mutations in the PNPLA6 gene in four index patients. Here we present two novel unrelated patients with BNS, where we identified four recessive PNPLA6 mutations (3 of them novel) as the genetic cause, using a targeted high-throughput approach. This finding provides the first replication from independent families that BNS is caused by PNPLA6 and, moreover, highlights PNPLA6 as the major gene leading to BNS. Given the fact that the major gene causing BNS has thus now been identified, we summarize the spectrum of clinical presentations and phenotype evolution of BNS based on a systematic in-depth review of the literature of previously published cases (n = 40). Both the two cases presented here and our review of the literature propose that the clinical presentation of BNS can be variable regarding both the age (ranging from 1 to 40 years) and the clinical symptoms at onset (cerebellar ataxia in 38 %; vision loss in 36 %; delayed puberty in 26 %). A substantial fraction of BNS cases may present with relatively selective atrophy of the superior and dorsal parts of the cerebellar vermis along with atrophy of the cerebellar hemispheres on MRI, while brainstem or cortical changes on MRI seem to be present only in small fractions. Also in the literature, no other major genetic causes of BNS other than PNPLA6 mutations were identified.