Exome analysis identified a novel missense mutation in the CLPP gene in a consanguineous Saudi family expanding the clinical spectrum of Perrault Syndrome type-3
Exome analysis identified a novel missense mutation in the CLPP gene in a consanguineous Saudi family expanding the clinical spectrum of Perrault Syndrome type-3
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DOI：
10.1016/j.jns.2015.04.038
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发表时间：
2015-06-15
影响因子：
4.4
通讯作者：
Al-Aama, Jumana Yousuf
中科院分区：
文献类型：
--
作者：
Ahmed, Saleem;Jelani, Musharraf;Al-Aama, Jumana Yousuf
佩罗综合征（PRLTS）是一种临床和遗传异质性疾病。男性和女性患者在儿童早期均患有感觉神经性听力损失，女性患者的特点是卵巢早衰和青春期后不孕。在生命早期可能无法进行临床诊断，因为 PLTS 的关键特征，例如不孕和卵巢早衰，在青春期之前不会出现。在 PLTS 患者中还观察到肢体痉挛、肌肉无力和智力障碍。据报道，PRLTS 的 5 种亚型中存在 5 种基因突变：HSD17B4、HARS2、CLPP、LARS2 和 C10orf2。我们发现了一个具有 PLTS3 表型的沙特近亲家族，显示出常染色体隐性遗传模式。这些患者在儿童早期就出现了严重的听力损失、脑萎缩和下肢痉挛。对于分子诊断，我们通过全外显子组测序分析补充了全基因组纯合性图谱，并在染色体 19p13.3 的 CLPP 外显子 6 中发现了一个新的纯合突变。据我们所知，早发且消退是这些PRLTS患者的独特特征，但迄今为止尚未有报道。这项研究拓宽了 PLTS3 的临床范围。 (C) 2015 Elsevier B.V. 保留所有权利。
Perrault syndrome (PRLTS) is a clinically and genetically heterogeneous disorder. Both male and female patients suffer from sensory neuronal hearing loss in early childhood, and female patients are characterized by premature ovarian failure and infertility after puberty. Clinical diagnosis may not be possible in early life, because key features of PRLTS, for example infertility and premature ovarian failure, do not appear before puberty. Limb spasticity, muscle weakness, and intellectual disability have also been observed in PRLTS patients. Mutations in five genes, HSD17B4, HARS2, CLPP, LARS2, and C10orf2, have been reported in five subtypes of PRLTS. We discovered a consanguineous Saudi family with the PRLTS3 phenotype showing an autosomal recessive mode of inheritance. The patients had developed profound hearing loss, brain atrophy, and lower limb spasticity in early childhood. For molecular diagnosis, we complimented genome-wide homozygosity mapping with whole exome sequencing analyses and identified a novel homozygous mutation in exon 6 of CLPP at chromosome 19p13.3. To our knowledge, early onset with regression is a unique feature of these PRLTS patients that has not been reported so far. This study broadens the clinical spectrum of PRLTS3. (C) 2015 Elsevier B.V. All rights reserved.