Univ. Limoges, MMNP, Limoges, France.
CHU Limoges, Service Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, Limoges, France.
Mol Genet Genomic Med. 2019 Sep;7(9):e875. doi: 10.1002/mgg3.875. Epub 2019 Jul 23.
CMTX5 is characterized by peripheral neuropathy, early-onset sensorineural hearing impairment, and optic neuropathy. Only seven variants have been reported and no genotype-phenotype correlations have yet been established. PRPS1 has a crystallographic structure, as it is composed of three dimers that constitute a hexamer.
Next-generation sequencing (NGS) was performed using a custom 92-gene panel designed for the diagnosis of Charcot-Marie-Tooth (CMT) and associated neuropathies.
We report the case of a 35-year-old male, who had presented CMT and hearing loss since childhood associated to bilateral optic neuropathy without any sign of retinitis pigmentosa. A new hemizygous variant on chromosomic position X:106,882,604, in the PRPS1 gene, c.202A > T, p.(Met68Leu) was found. This change is predicted to lead to an altered affinity between the different subunits in the dimer, thereby may prevent the hexamer formation.
CMTX5 is probably under-diagnosed, as an overlap among the different features due to PRPS1 exists. Patients who developed polyneuropathy associated to sensorineural deafness and optic atrophy during childhood should be assessed for PRPS1.
CMTX5 的特征是周围神经病、早发性感觉神经性听力损失和视神经病变。仅报道了七种变体，尚未建立基因型-表型相关性。PRPS1 具有晶体结构，因为它由三个构成六聚体的二聚体组成。
使用针对 Ch arcot-Marie-Tooth (CMT) 和相关神经病变诊断设计的定制 92 基因面板进行下一代测序 (NGS)。
我们报告了一名 35 岁男性的病例，他自童年起就出现 CMT 和听力损失，伴有双侧视神经病变，而没有任何视网膜色素变性的迹象。在 PRPS1 基因中，在染色体位置 X:106,882,604 处发现了一个新的半合子变体 c.202A>T，p.(Met68Leu)。该变化预计会导致二聚体之间不同亚基之间的亲和力改变，从而可能阻止六聚体的形成。
CMTX5 可能诊断不足，因为 PRPS1 存在不同特征之间的重叠。在儿童期出现多发性神经病伴感觉神经性耳聋和视神经萎缩的患者应评估 PRPS1。
