Compound heterozygous PNPLA6 mutations cause Boucher-Neuhäuser syndrome with late-onset ataxia.
Compound heterozygous PNPLA6 mutations cause Boucher-Neuhäuser syndrome with late-onset ataxia.
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DOI：
10.1007/s00415-014-7516-3
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发表时间：
2014-12
影响因子：
6
通讯作者：
Paisán-Ruiz C
中科院分区：
文献类型：
--
作者：
Deik A;Johannes B;Rucker JC;Sánchez E;Brodie SE;Deegan E;Landy K;Kajiwara Y;Scelsa S;Saunders-Pullman R;Paisán-Ruiz C
PNPLA6突变，已知与运动神经元表型的发展有关，最近在Boucher-Neuhäuser综合征家族中被发现。Boucher-Neuhäuser是一种罕见的常染色体隐性综合征，以小脑共济失调、促性腺功能低下和绒毛膜视网膜营养不良共同发生为特征。Boucher-Neuhäuser的步态共济失调通常在成年早期表现出来，尽管也有报道称在第三或第四个十年发病。然而，鉴于最近发现PNPLA6突变是导致这种情况的原因，仍然需要确定症状发病年龄的决定因素。在这里，我们已经确定了一个散发Boucher-Neuhäuser病例迟发性步态共济失调和相对较轻的视网膜变化，由于复合杂合PNPLA6突变。从患者基因组DNA编码外显子26-29进行克隆和测序，证实了复合杂合性。此外，两种突变（一种是新的，一种是已知的）都位于磷脂酶酯酶结构域，而大多数致病突变似乎都聚集在这里。综上所述，我们在此证实PNPLA6突变是Boucher-Neuhäuser综合征的主要原因，并建议在出现迟发性步态共济失调的患者中询问性腺功能减退或视力改变的病史。我们也提倡对疑似病例进行神经眼科评估。
PNPLA6 mutations, known to be associated with the development of motor neuron phenotypes, have recently been identified in families with Boucher–Neuhäuser syndrome. Boucher–Neuhäuser is a rare autosomal recessive syndrome characterized by the co-occurrence of cerebellar ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. Gait ataxia in Boucher–Neuhäuser usually manifests before early adulthood, although onset in the third or fourth decade has also been reported. However, given the recent identification of PNPLA6 mutations as the cause of this condition, the determining factors of age of symptom onset still need to be established. Here, we have identified a sporadic Boucher–Neuhäuser case with late-onset gait ataxia and relatively milder retinal changes due to compound heterozygous PNPLA6 mutations. Compound heterozygosity was confirmed by cloning and sequencing the patient’s genomic DNA from coding exons 26–29. Furthermore, both mutations (one novel and one known) fell in the phospholipase esterase domain, where most pathogenic mutations seem to cluster. Taken together, we herein confirm PNPLA6 mutations as the leading cause of Boucher–Neuhäuser syndrome and suggest inquiring about a history of hypogonadism or visual changes in patients presenting with late-onset gait ataxia. We also advocate for neuroophthalmologic evaluation in suspected cases.
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影响因子：
4.3
作者：
Bendl J;Stourac J;Salanda O;Pavelka A;Wieben ED;Zendulka J;Brezovsky J;Damborsky J
通讯作者：
Damborsky J
影响因子：
3.5
作者：
Emerick, Guilherme L.;Peccinini, Rosangela G.;de Oliveira, Georgino H.
通讯作者：
de Oliveira, Georgino H.
影响因子：
5.3
作者：
Read, David J.;Li, Yong;Glynn, Paul
通讯作者：
Glynn, Paul
影响因子：
3.7
作者：
Krebs CE;Paisán-Ruiz C
通讯作者：
Paisán-Ruiz C
影响因子：
3.2
作者：
Quinton, R;Barnett, P;Bouloux, PMG
通讯作者：
Bouloux, PMG