Support for the 1st International Basic Science and Clinical Conference on Christianson Syndrome

 描述（由申请人提供）：Christianson综合征（CS）是最近发现的X连锁神经发育障碍，由编码钠-氢交换剂（称为NHE 6）的SLC 9A 6中的有害突变引起。该蛋白质与其他8种NHE蛋白质沿着是溶质载体家族的成员，被发现定位于细胞中的不同膜，在那里它们被认为影响管腔区域的pH。NHE 6与早期内体和再循环内体相关，并且最近对敲除小鼠模型的研究已经显示出生长因子信号传导、神经递质受体循环以及溶酶体功能的缺陷。临床上，CS患者可通过智力障碍、共济失调、癫痫、最小言语状态、出生后小头畸形和小脑变性的特征来识别。一些患者也具有自闭症特征。在鉴定CS基因之前，“快乐行为”的存在通常导致Angelman综合征的诊断，因此被称为X连锁Angelman样综合征。重要的是，迄今为止描述的CS男性患有癫痫，癫痫发作类型包括：婴儿痉挛、强直性癫痫发作、强直阵挛性癫痫发作、肌阵挛性癫痫发作、跌倒发作和描述为凝视发作的发作。迄今为止，对女性CS携带者的临床参与分析较少。虽然CS是一种罕见的疾病，但Morrow及其同事已经确定了21个受影响的家庭和26个人，其中包括来自美国，加拿大和欧洲的家庭和患者。2011年，德克萨斯州休斯顿的一个家庭成立了一个克里斯蒂安森综合症协会（CSA），现在加拿大也成立了一个类似的组织。CSA于2013年在布朗大学举行了首次会议（由Eric Morrow博士主持），将感兴趣的临床医生和科学家的家庭聚集在一起。加空局强烈支持在2015年家庭会议期间举办一次国际科学会议，这项建议的目的是确保为这一活动提供资金。本次会议计划由不同的知名演讲者和CS专家-国家和国际，包括神经发育和癫痫发作障碍领域的领导者的演讲。我们还期待为包括女性和少数民族在内的初级研究人员创造有影响力的机会，以参与科学交流并与CS患者及其家属会面。预计这次会议的主要成果包括：（i）建立合作研究和临床推广计划的网络和建立;（ii）产生关于CS发病机制和可能治疗的新想法，包括研究和合作赠款的新途径;（iii）扩大CS研究和临床社区，包括向初级科学家和临床医生介绍研究CS和其他相关疾病的重要性。 罕见疾病;以及（iv）建立国际CS研究和临床网络，以促进全面合作，多实验室基础研究，并鼓励启动患者登记和自然史研究，以促进患者护理和治疗。

 DESCRIPTION (provided by applicant): Christianson syndrome (CS) is a recently discovered X-linked neurodevelopmental disorder caused by deleterious mutations in SLC9A6 which encodes the sodium-hydrogen exchanger known as NHE6. This protein, along with 8 other NHE proteins, are members of the family of solute carriers found localized to different membranes in cells where they are thought to influence the pH of luminal areas. NHE6 is associated with early endosomes and recycling endosomes and recent studies of a knockout mouse model have shown defects in growth factor signaling, neurotransmitter receptor cycling as well as in lysosomal function. Patients with CS are clinically recognized by features of intellectual disability, ataxia, epilepsy, minimal verbal status, postnatal microcephaly, and cerebellar degeneration. Autistic features have also been ascribed to some patients. Prior to identification of the CS gene, the presence of a `happy demeanor' typically led to a diagnosis of Angelman syndrome, and thus was referred to as X-linked Angelman-like syndrome. Importantly, males with CS described to date have epilepsy, with seizure types including: infantile spasms, tonic seizures, tonic-clonic seizures, myoclonic seizures, drop seizures, and episodes described as staring spells. Clinical involvement in female carriers of CS has been less closely analyzed to date. While CS is a rare condition, Morrow and colleagues have identified 21 affected families and 26 individuals, which include families and patients from the United States, Canada, and Europe. A Christianson Syndrome Association (CSA) was formed in 2011 by a family in Houston, Texas, and a similar organization has now been established in Canada. The CSA held an initial meeting at Brown University in 2013 (hosted by Dr. Eric Morrow) that brought together families with interested clinicians and scientists. The CSA strongly supports the inclusion of an international scientific conference in conjunction with its 2015 family meeting and the purpose of this proposal is to secure funding to facilitate this event. Planned for this meeting are presentations from a diverse array of well-known speakers and CS experts - national and international, including leaders in the field of neurodevelopmental and seizure disorders. We also anticipate the creation of impactful opportunities for junior investigators, including women and minorities, to participate in scientific exchange and to meet CS patients and their families. Key outcomes expected from this meeting include: (i) networking and establishment of collaborative research and clinical outreach programs; (ii) generation of new ideas on the pathogenesis and possible treatment of CS, including new avenues of research and collaborative grants; (iii) expansion of the CS research and clinical community, including the introduction of junior scientists and clinicians to the importance of studying CS and other related rare diseases; and (iv) establishment of an international CS research and clinical network to foster fully collaborative, multi-laboratory basic research and to encourage initiation of a patien registry and natural history study in order to advance patient care and treatment.