Whole-genome sequencing revealed armadillo repeat containing 5 (ARMC5) mutation in a Chinese family with ACTH-independent macronodular adrenal hyperplasia
-
- Zhang Qian
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China Department of Endocrinology, PLA Army General Hospital, Beijing 100700, China
-
- Cui Liang
- Department of Urinary Surgery, Civil Aviation General Hospital, Beijing 100123, China
-
- Gao Jiang-Ping
- Department of Urinary Surgery, Chinese PLA General Hospital, Beijing 100853, China
-
- Yan Wen-Hua
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Jin Nan
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Chen Kang
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Zang Li
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Du Jin
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Wang Xian-Ling
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Guo Qing-Hua
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Yang Guo-Qing
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Yang Li-Juan
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Ba Jian-Ming
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Gu Wei-Jun
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Lv Zhao-Hui
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Dou Jing-Tao
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Mu Yi-Ming
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
-
- Lu Ju-Ming
- Department of Endocrinology, Chinese PLA General Hospital, Beijing 100853, China
この論文をさがす
抄録
<p>Primary macronodular adrenal hyperplasia (PMAH), also known in the past as bilateral macronodular adrenalhyperplasia or adrenocorticotropin (ACTH)-independent macronodular adrenal hyperplasia, is a rare type of Cushing’s syndrome (CS) and is associated with bilateralenlargement of the adrenal glands. It accounts for <1% of all endogenous cases of CS. In order toidentify the pathogenic mutations in the causative gene of (AIMAH pedigrees, Whole-genome sequencing of three patients in family I was used to retrieve candidate causative genes. Meanwhile, the causative gene was identified by Sanger sequencing from the two pedigrees. Sequencing of ARMC5 exons of three patients was carried out to identify somatic mutations. Moreover, haploid clone of one tumor DNA sample was conducted. ARMC5 was the causative gene of two pedigrees confirmed by whole-genome sequencing (WGA) and Sanger sequencing. The variant sites of the two families were c.C943T (p.R315W) and c.C1960T (p.R654X), respectively. Autosomal dominant inheritance of AIMAH was confirmed by genotypes of one family member. Several somatic mutations were discovered in tumor DNA samples. In addition, haploid clone of tumor DNA was confirmed by germline mutation and somaticmutation, which suggested the pathogenic mechanism of “two-hit-model.” ARMC5 was the causative gene of AIMAH pedigrees. This AIMAH in this study presented autosomal dominant inheritance, fitting to Mendelian inheritance law. However, the pathogenic mode of this disease showed as compound heterozygote.</p>
収録刊行物
-
- Endocrine Journal
-
Endocrine Journal 65 (3), 269-279, 2018
一般社団法人 日本内分泌学会