PYCR2 Mutations cause a lethal syndrome of microcephaly and failure to thrive.
PYCR2 Mutations cause a lethal syndrome of microcephaly and failure to thrive.
复制标题
PYCR2突变会导致小头畸形的致命综合征和未能繁殖。
DOI：
10.1002/ana.24678
复制
发表时间：
2016-07
影响因子：
11.2
通讯作者：
Gleeson JG
中科院分区：
文献类型：
--
作者：
Zaki MS;Bhat G;Sultan T;Issa M;Jung HJ;Dikoglu E;Selim L;G Mahmoud I;Abdel-Hamid MS;Abdel-Salam G;Marin-Valencia I;Gleeson JG
进行了一项研究，以描述新描述的10型脑白质营养不良伴小头畸形的临床特征。这是一种常染色体隐性遗传疾病，定位于染色体1q42.12，由于PYCR 2基因突变，编码一种参与线粒体中脯氨酸合成的酶。从几个国际诊所，11个血缘家庭被确定为PYCR2突变的全外显子组或靶向测序，详细的临床和放射学表型。测试来自患者的选择性突变对蛋白质功能的影响。PYCR 2突变患者的特征性临床表现包括发育不良、小头畸形、颅面畸形、进行性精神残疾、运动过度和轴性肌张力减退伴可变性无脑痉挛。患者不能存活超过生命的第一个十年。脑磁共振成像（MRI）显示全脑萎缩和白色T2高信号。常规血清代谢特征不显著。无义突变和错义突变都被鉴定，这损害了蛋白质的多聚化。PYCR 2相关综合征是一种临床可识别的疾病，其中PYCR 2突变导致蛋白质功能障碍，常规生化评估无法检测到。突变预示预后不良，可能是线粒体功能受损的结果。
A study was undertaken to characterize the clinical features of the newly described hypomyelinating leukodystrophy type 10 with microcephaly. This is an autosomal recessive disorder mapped to chromosome 1q42.12 due to mutations in PYCR2 gene, encoding an enzyme involved in proline synthesis in mitochondria. From several international clinics, eleven consanguineous families were identified with PYCR2 mutations by whole exome or targeted sequencing, with detailed clinical and radiological phenotyping. Selective mutations from patients were tested for effect on protein function. The characteristic clinical presentation of patients with PYCR2 mutations included failure to thrive, microcephaly, craniofacial dysmorphism, progressive psychomotor disability, hyperkinetic movements, and axial hypotonia with variable appendicular spasticity. Patients did not survive beyond the first decade of life. Brain magnetic resonance imaging (MRI) showed global brain atrophy and white matter T2 hyperintensities. Routine serum metabolic profiles were unremarkable. Both nonsense and missense mutations were identified, which impaired protein multimerization. PYCR2-related syndrome represents a clinically recognizable condition in which PYCR2 mutations lead to protein dysfunction, not detectable on routine biochemical assessments. Mutations predict a poor outcome, probably as a result of impaired mitochondrial function.