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

 描述（由申请人提供）：克里斯蒂安森综合征（CS）是最近发现的一种 X 连锁神经发育障碍，由 SLC9A6 的有害突变引起，SLC9A6 编码称为 NHE6 的钠氢交换体。这种蛋白质与其他 8 种 NHE 蛋白质一样，属于溶质载体家族的成员，这些蛋白质分布在细胞的不同膜上，被认为会影响管腔区域的 pH 值。 NHE6 与早期内体和再循环内体相关，最近对基因敲除小鼠模型的研究表明，生长因子信号传导、神经递质受体循环以及溶酶体功能存在缺陷。临床上，CS 患者的特征是智力障碍、共济失调、癫痫、语言障碍、出生后小头畸形和小脑变性。一些患者也被认为患有自闭症。在鉴定出 CS 基因之前，“快乐举止”的存在通常会导致天使综合征的诊断，因此被称为 X 连锁天使综合征。重要的是，迄今为止描述的患有CS的男性患有癫痫，癫痫发作类型包括：婴儿痉挛症、强直性癫痫发作、强直阵挛性癫痫发作、肌阵挛性癫痫发作、跌倒性癫痫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还较少。虽然 CS 是一种罕见疾病，但 Morrow 和同事已经确定了 21 个受影响的家庭和 26 名个人，其中包括来自美国、加拿大和欧洲的家庭和患者。德克萨斯州休斯顿的一个家庭于 2011 年成立了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（由埃里克·莫罗博士主持），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 年家庭会议的同时举办一次国际科学会议，该提案的目的是确保为促进该活动提供资金。计划在本次会议上发表演讲的有国内外众多知名演讲者和计算机科学专家，其中包括神经发育和癫痫领域的领导者。我们还期望为初级研究人员（包括女性和少数族裔）创造有影响力的机会，让他们参与科学交流并会见 CS 患者及其家人。本次会议预计取得的主要成果包括：(i) 建立网络并建立合作研究和临床推广计划； (ii) 产生关于 CS 发病机制和可能治疗的新想法，包括新的研究途径和合作资助； (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 和其他相关的重要性 罕见疾病； (iv) 建立国际 CS 研究和临床网络，以促进充分协作、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.