Clinical and genetic analysis of two Chinese infants with Mabry syndrome
Clinical and genetic analysis of two Chinese infants with Mabry syndrome
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DOI：
10.1016/j.braindev.2016.04.008
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发表时间：
2016-10-01
影响因子：
1.7
通讯作者：
Yang, Zhixian
中科院分区：
文献类型：
--
作者：
Xue, Jiao;Li, Hui;Yang, Zhixian
目的：高磷酸酯酶症智力低下综合征（马布里综合征）是一种常染色体隐性遗传疾病。我们旨在分析两例诊断为马布里综合征的中国患者。方法：观察两例患者的临床表现、诊断和治疗。进行PIGV、PIGO等基因分析。结果：2例患者经临床和遗传学确诊为马布里综合征。两人均出现发育迟缓、磷酸酯酶过多和癫痫发作。典型的面部畸形和末端指骨发育不全仅1例出现。 2例患者出现先天性喉软骨软化、腹股沟疝、掌纹破裂、视神经萎缩、腕骨年龄延迟、形而上异常等骨骼发育不良等新表现。分子遗传学分析显示，我们的患者存在 PIGV 或 PIGO 的复合杂合突变，包括患者 1 中 PIGV 的 c.615C > G (p.Asn205Lys) 和 c.854A > G (p.Tyr285Cys)，以及 c.458T > C (p.Phe153Ser) 和 c.1355_1356del患者2的PIGO (p.Ala452Glyfs*52)。此外，在携带PIGV突变的患者中鉴定出PCDH19的杂合c.2926G > A (Asp976Asn)，PIGV突变是女性癫痫和智力低下的致病基因(EFMR)。结论：据我们所知，这是首次报告诊断为马布里综合征的中国患者。对于本例携带PIGV突变的患者的PCDH19突变，由于缺乏EFMR特征以及致病性分析结果的模糊性，我们不确定PCDH19突变与PIGV突变在该疾病中的致病作用有多大。本文报道的 PIGV 和 PIGO 的新突变以及新的临床表现可能会扩大 Mabry 综合征的基因型和表型谱。 (C) 2016 年日本儿童神经病学学会。由 Elsevier B.V. 出版。保留所有权利。
Objective: Hyperphosphatasia mental retardation syndrome (Mabry syndrome) is an autosomal recessive disorder. We aim to analyze two Chinese patients diagnosed as Mabry syndrome.Methods: The clinical manifestations, diagnosis and treatment were observed in two patients. Genetic analysis including PIGV and PIGO was examined.Results: Two patients were diagnosed as Mabry syndrome clinically and genetically. Developmental delay, hyperphosphatasia and seizures were presented in both of them. Typical facial dysmorphism and hypoplastic terminal phalanges were only found in one. Some novel presentations including congenital laryngeal cartilage softening, inguinal hernia, broken palmprint, optic atrophy and skeleton dysplasia such as carpal age delay and metaphysic anomalies were observed in two patients. Molecular genetic analysis revealed compound heterozygous mutations of PIGV or PIGO in our patients, including c.615C > G (p.Asn205Lys) and c.854A > G (p.Tyr285Cys) of PIGV in patient 1, and c.458T > C (p.Phe153Ser) and c.1355_1356del (p.Ala452Glyfs*52) of PIGO in patient 2. Additionally, a heterozygous c.2926G > A (Asp976Asn) of PCDH19 was identified in patient with PIGV mutations, the causative gene of Epilepsy and mental retardation limited to females (EFMR).Conclusion: To our best knowledge, this is the first time to report Chinese patients diagnosed as Mabry syndrome. For the PCDH19 mutation in our patient carrying PIGV mutations, due to lacking characteristics of EFMR and the ambiguity results in pathogenicity analysis, we were not sure how much pathogenic role PCDH19 mutation shared with PIGV mutations in this disease. The novel mutations of PIGV and PIGO, and novel clinical manifestations reported here might expand the genotype and phenotype spectrum of Mabry syndrome. (C) 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.