PDF(Pubmed)
Abstract：
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and poikiloderma in association with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) are rare inherited syndromes resulting from biallelic pathogenic variants in AIRE and heterozygous pathogenic variants in FAM111B, respectively. The clinical diagnosis of APECED and POIKTMP rely on the development of two or more characteristic disease manifestations that define the corresponding syndromes. We discuss the shared and distinct clinical, radiographic, and histological features between APECED and POIKTMP presented in our patient case and describe his treatment response to azathioprine for POIKTMP-associated hepatitis, myositis, and pneumonitis.
Through informed consent and enrollment onto IRB-approved protocols (NCT01386437, NCT03206099) the patient underwent a comprehensive clinical evaluation at the NIH Clinical Center alongside exome sequencing, copy number variation analysis, autoantibody surveys, peripheral blood immunophenotyping, and salivary cytokine analyses.
We report the presentation and evaluation of a 9-year-old boy who was referred to the NIH Clinical Center with an APECED-like clinical phenotype that included the classic APECED dyad of CMC and hypoparathyroidism. He was found to meet clinical diagnostic criteria for POIKTMP featuring poikiloderma, tendon contractures, myopathy, and pneumonitis, and exome sequencing revealed a de novo c.1292T>C heterozygous pathogenic variant in FAM111B but no deleterious single nucleotide variants or copy number variants in AIRE.
This report expands upon the available genetic, clinical, autoantibody, immunological, and treatment response information on POIKTMP.
Through informed consent and enrollment onto IRB-approved protocols (NCT01386437, NCT03206099) the patient underwent a comprehensive clinical evaluation at the NIH Clinical Center alongside exome sequencing, copy number variation analysis, autoantibody surveys, peripheral blood immunophenotyping, and salivary cytokine analyses.
We report the presentation and evaluation of a 9-year-old boy who was referred to the NIH Clinical Center with an APECED-like clinical phenotype that included the classic APECED dyad of CMC and hypoparathyroidism. He was found to meet clinical diagnostic criteria for POIKTMP featuring poikiloderma, tendon contractures, myopathy, and pneumonitis, and exome sequencing revealed a de novo c.1292T>C heterozygous pathogenic variant in FAM111B but no deleterious single nucleotide variants or copy number variants in AIRE.
This report expands upon the available genetic, clinical, autoantibody, immunological, and treatment response information on POIKTMP.
摘要：
未经证实：自身免疫性多内分泌病-念珠菌病-外胚层营养不良（APECED）和与肌腱挛缩相关的多毛皮病，肌病,和肺纤维化（POIKTMP）是罕见的遗传综合征，由AIRE的双等位基因致病性变异和FAM111B的杂合致病性变异引起，分别。APECED和POIKTMP的临床诊断依赖于定义相应综合征的两种或多种特征性疾病表现的发展。我们讨论了共同和独特的临床，射线照相,和APECED和POIKTMP之间的组织学特征，并描述了他对硫唑嘌呤对POIKTMP相关肝炎的治疗反应，肌炎,和肺炎。
UASSIGNED：通过知情同意和纳入IRB批准的方案（NCT01386437，NCT03206099），患者在NIH临床中心进行了全面的临床评估，同时进行了外显子组测序，拷贝数变异分析，自身抗体调查，外周血免疫分型,和唾液细胞因子分析。
UNASSIGNED：我们报告了一名9岁男孩的报告和评估，该男孩被转诊到美国国立卫生研究院临床中心，具有APECED样临床表型，包括经典的APECEDCMC和甲状旁腺功能减退。他被发现符合以真皮病为特征的POIKTMP的临床诊断标准，肌腱挛缩,肌病,和肺炎，和外显子组测序显示FAM111B中的从头c.1292T>C杂合致病变异，但AIRE中没有有害的单核苷酸变异或拷贝数变异。
未经评估：本报告扩展了现有的遗传，临床,自身抗体,免疫学，以及关于POIKTMP的治疗反应信息。
UASSIGNED：通过知情同意和纳入IRB批准的方案（NCT01386437，NCT03206099），患者在NIH临床中心进行了全面的临床评估，同时进行了外显子组测序，拷贝数变异分析，自身抗体调查，外周血免疫分型,和唾液细胞因子分析。
UNASSIGNED：我们报告了一名9岁男孩的报告和评估，该男孩被转诊到美国国立卫生研究院临床中心，具有APECED样临床表型，包括经典的APECEDCMC和甲状旁腺功能减退。他被发现符合以真皮病为特征的POIKTMP的临床诊断标准，肌腱挛缩,肌病,和肺炎，和外显子组测序显示FAM111B中的从头c.1292T>C杂合致病变异，但AIRE中没有有害的单核苷酸变异或拷贝数变异。
未经评估：本报告扩展了现有的遗传，临床,自身抗体,免疫学，以及关于POIKTMP的治疗反应信息。
