Gursoy Semra, Ataman Esra, Baysal Bahar Toklu, Özyılmaz Berk, Gençpınar Pınar, Hız Ayşe Semra, Yiş Uluç, Ünalp Aycan, Dündar Nihal Olgaç, Ülgenalp Ayfer, Erçal Derya
Department of Pediatric Genetics, Dr. Behcet Uz Children's Hospital, Izmir, Turkey.
Department of Medical Genetics, Dokuz Eylül University Medical School, Izmir, Turkey.
Ann Indian Acad Neurol. 2020 Mar-Apr;23(2):206-210. doi: 10.4103/aian.AIAN_465_19. Epub 2020 Feb 25.
gene, which encodes protocadherin 19, is associated with epilepsy and intellectual disability, mainly in affected females. The clinical manifestations are heterogeneous and the main features include early onset seizure, generalized or focal seizures sensitive to fever, and brief seizures occurring in clusters. The disorders exhibit a unique and unusual X-linked pattern of expression. We aimed to investigate mutations/deletions in patients with epilepsy and describe the clinical/molecular features.
gene was analyzed in 35 Turkish female patients from 34 families with early-onset epilepsy via direct sequencing and multiplex ligation-dependent probe amplification analysis. Additionally, array comparative genomic hybridization analysis was performed in patients with whole gene deletion.
We identified 2 different heterozygous mutations in 2 unrelated probands (5. 7%) which were located in exon 1. Additionally, whole gene deletions were detected in dizygotic twin girls (5. 7%), who had distinct clinical features and the deletion was inherited from the unaffected father. The second twin suffered more severe clinical manifestations including autistic features, behavioral problems, mild-moderate mental retardation and seizures, which were under control with multidrug regimen when compared with the first twin.
is a major causative gene in patients with epilepsy and further data is required to gain a better understanding of phenotype-genotype correlation. In addition to gene sequencing, deletion/duplication analysis will improve the molecular diagnosis in patients with clinical findings.
编码原钙黏蛋白19的基因与癫痫和智力残疾相关，主要见于受影响的女性。临床表现具有异质性，主要特征包括早发性癫痫、对发热敏感的全身性或局灶性癫痫发作以及成簇出现的短暂癫痫发作。这些疾病呈现出独特且不寻常的X连锁表达模式。我们旨在研究癫痫患者的突变/缺失情况，并描述其临床/分子特征。
通过直接测序和多重连接依赖探针扩增分析，对来自34个早发性癫痫家族的35名土耳其女性患者的该基因进行分析。此外，对全基因缺失的患者进行了阵列比较基因组杂交分析。
我们在2名无关的先证者中鉴定出2种不同的杂合突变（5.7%），位于外显子1。此外，在双卵双胞胎女孩中检测到全基因缺失（5.7%），她们具有不同的临床特征，缺失从未受影响的父亲遗传而来。与第一个双胞胎相比，第二个双胞胎的临床表现更严重，包括自闭症特征、行为问题、轻度至中度智力发育迟缓以及癫痫发作，通过多药治疗方案可得到控制。
该基因是癫痫患者的主要致病基因，需要更多数据以更好地理解表型 - 基因型相关性。除了基因测序外，缺失/重复分析将改善具有临床症状患者的分子诊断。
