Gozes Illana, Patterson Marc C, Van Dijck Anke, Kooy R Frank, Peeden Joseph N, Eichenberger Jacob A, Zawacki-Downing Angela, Bedrosian-Sermone Sandra
The Lily and Avraham Gildor Chair for the Investigation of Growth Factors, Elton Laboratory for Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Adams Super Center for Brain Studies and Sagol School for Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Division of Child and Adolescent Neurology, Pediatrics and Medical Genetics, Mayo Clinic Children's Center Rochester, Rochester, MN, USA.
Front Endocrinol (Lausanne). 2017 May 19;8:107. doi: 10.3389/fendo.2017.00107. eCollection 2017.
Activity-dependent neuroprotective protein (ADNP) is one of the most prevalent mutated genes in syndromic autism spectrum disorders, driving a general interest in the gene and the syndrome.
The aim of this study was to provide a detailed developmental case study of ADNP p.Tyr719* mutation toward improvements in (1) diagnostic procedures, (2) phenotypic scope, and (3) interventions.
Longitudinal clinical and parental reports.
AD (currently 11-year-old) had several rare congenital anomalies including imperforate anus that was surgically repaired at 2 days of age. Her findings were craniofacial asymmetries, global developmental delay, autistic behaviors (loss of smile and inability to make eye contact at the age of 15 months), and slow thriving as she gradually matures. Comprehensive diagnostic procedures at 3 years resulted in no definitive diagnosis. With parental persistence, AD began walking at 3.5 years (skipping crawling). At the age of 8.5 years, AD was subjected to whole exome sequencing, compared to the parents and diagnosed as carrying an ADNP p.Tyr719* mutation, a causal recurring mutation in ADNP (currently ~17/80 worldwide). Brain magnetic resonance imaging demonstrated mild generalized cerebral volume loss with reduced posterior white matter. AD is non-verbal, communicating with signs and word approximations. She continues to make slow but forward developmental progress, and her case teaches newly diagnosed children within the ADNP Kids Research Foundation.
This case study emphasizes the importance of diagnosis and describes, for the first time, early motor intervention therapies. Detailed developmental profile of selected cases leads to better treatments.
活性依赖神经保护蛋白（ADNP）是综合征性自闭症谱系障碍中最常见的突变基因之一，引发了人们对该基因及相关综合征的广泛关注。
本研究旨在提供一个关于ADNP p.Tyr719*突变的详细发育病例研究，以促进（1）诊断程序、（2）表型范围和（3）干预措施的改进。
纵向临床和家长报告。
AD（目前11岁）有多种罕见的先天性异常，包括肛门闭锁，出生2天时接受了手术修复。她的表现有颅面不对称、全面发育迟缓、自闭症行为（15个月大时失去微笑且无法进行眼神交流），随着逐渐长大，生长缓慢。3岁时进行的全面诊断程序未得出明确诊断。在家长的坚持下，AD在3.5岁时开始走路（跳过爬行阶段）。8.5岁时，AD接受了全外显子测序，与父母进行比较后，被诊断为携带ADNP p.Tyr719*突变，这是ADNP中一种反复出现的致病突变（目前全球约17/80）。脑磁共振成像显示轻度广泛性脑容量减少，后部白质减少。AD不会说话，通过手势和近似单词进行交流。她继续缓慢但持续地取得发育进展，她的病例为ADNP儿童研究基金会内新诊断的儿童提供了借鉴。
本病例研究强调了诊断的重要性，并首次描述了早期运动干预疗法。对特定病例的详细发育概况研究有助于更好地进行治疗。
