PDF(Pubmed)
Abstract：
BACKGROUND X-linked intellectual disabilities constitute a group of clinically and genetically heterogeneous disorders that are divided into syndromic and nonsyndromic forms. PAK3 mutations are associated with X-linked nonsyndromic forms of intellectual disability, with the most common clinical features being cognitive deficit, large ears, oral motor hypotonia, and neurobehavioral abnormalities. These mutations have been reported to be associated with either loss of the PAK3 protein or loss of its kinase activity. We report a case with the novel PAK3 variant c.685C>T p.(Pro229Ser), which has not been previously described. CASE REPORT We report the first case of a PAK3 mutation to present with the common clinical features along with immunodeficiency resembling common variable immune deficiency. Our patient was a 10-year-old girl who had experienced septic shock with a rapidly deteriorating course when she was 5-years-old. The initial immune work-up showed lymphopenia affecting all cell lines, but preferentially the B-cell compartment. Further work-up of this patient revealed low levels of immunoglobulin (Ig) G, undetectable IgA, reduced IgG1 and IgG2 subclasses, and poor response to the diphtheria/tetanus vaccine. Lymphocyte function, tested as the response to the mitogen phytohemagglutinin, was low and fluctuated between 9% and 22% compared with control samples. The patient experienced recurrent respiratory tract infections, and she responded well to regular intravenous Ig treatment and antibiotic prophylaxis. CONCLUSIONS The current case might provide a new insight into PAK3 gene function. Although further evidence is needed, it is worth considering that immunological abnormalities may be associated with PAK3 gene mutations.
摘要：
背景技术X连锁智力障碍构成一组临床和遗传异质性障碍,其分为综合征型和非综合征型。PAK3突变与X连锁的非综合征型智力障碍有关，最常见的临床特征是认知障碍，大耳朵,口腔运动性张力减退,和神经行为异常。据报道,这些突变与PAK3蛋白的丧失或其激酶活性的丧失有关。我们报告了一例新型PAK3变体c.685C>Tp。（Pro229Ser），以前没有描述过。病例报告我们报告了首例PAK3突变，具有共同的临床特征，并伴有类似于常见可变免疫缺陷的免疫缺陷。我们的患者是一名10岁的女孩，她在5岁时经历了感染性休克，病程迅速恶化。最初的免疫检查显示淋巴细胞减少影响所有细胞系，但优先考虑B细胞室。该患者的进一步检查显示免疫球蛋白（Ig）G水平低，检测不到IgA,减少IgG1和IgG2亚类，对白喉/破伤风疫苗的反应不佳。淋巴细胞功能，作为对有丝分裂原植物血凝素的反应，与对照样品相比，这一比例较低，波动在9%至22%之间。患者反复呼吸道感染,她对常规静脉注射Ig治疗和抗生素预防反应良好。结论目前的情况可能为PAK3基因功能提供了新的见解。虽然还需要进一步的证据,值得考虑的是,免疫异常可能与PAK3基因突变有关.
