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

 描述(申请人提供)：克里斯汀森综合征(CS)是最近发现的一种X连锁神经发育障碍，由编码钠氢交换蛋白NHE6的SLC9A6有害突变引起。该蛋白和其他8种NHE蛋白是溶质载体家族的成员，发现它们定位于细胞的不同膜上，在那里它们被认为影响管腔区域的pH值。NHE6与早期内小体和循环内小体有关，最近对基因敲除小鼠模型的研究表明，在生长因子信号、神经递质受体循环和溶酶体功能方面存在缺陷。CS患者的临床特征是智力残疾、共济失调、癫痫、最小的语言能力、出生后小头畸形和小脑变性。自闭症的特征也被归因于一些患者。在CS基因被鉴定之前，“快乐的举止”的出现通常会导致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，患有CS的男性被描述为癫痫，发作类型包括：婴儿痉挛、强直性发作、强直-阵挛发作、肌阵挛发作、滴性发作，以及被描述为凝视发作的发作。到目前为止，CS女性携带者的临床参与分析还较少。虽然CS是一种罕见的疾病，但Morrow和他的同事已经确定了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，德克萨斯州休斯敦的一个家庭成立了基督徒综合征协会(CSA)，加拿大现在也成立了类似的组织。CSA于2013年在布朗大学举行了第一次会议(由Eric Morrow博士主持)，将家庭与感兴趣的临床医生和科学家聚集在一起。CSA强烈支持在其2015年家庭会议的同时列入一次国际科学会议，这项提议的目的是获得资金，以促进这一活动。本次会议计划由国内和国际知名演讲者和CS专家发表演讲，其中包括神经发育和癫痫障碍领域的领导人。我们还期待为初级调查人员，包括妇女和少数族裔，创造有影响力的机会，参与科学交流，并会见CS患者及其家人。预期本次会议的主要成果包括：(I)建立网络并建立合作研究和临床推广计划；(Ii)就CS的发病机制和可能的治疗产生新的想法，包括新的研究途径和合作赠款；(Iii)扩大CS研究和临床社区，包括引入初级科学家和临床医生，使他们认识到研究CS和其他相关疾病的重要性 (Iv)建立国际CS研究和临床网络，以促进充分合作、多实验室的基础研究，并鼓励开展病人登记和自然病史研究，以促进病人的护理和治疗。

 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.