GERMLINE DELETION OF ARMC5 IN FAMILIAL PRIMARY MACRONODULAR ADRENAL HYPERPLASIA

被引:15
作者
Suzuki, Sawako [1 ]
Tatsuno, Ichiro [2 ]
Oohara, Emi [1 ]
Nakayama, Akitoshi [1 ]
Komai, Eri [1 ]
Shiga, Akina [1 ]
Kono, Takashi [1 ]
Takiguchi, Tomoko [1 ]
Higuchi, Seiichiro [1 ]
Sakuma, Ikki [1 ]
Nagano, Hidekazu [1 ]
Hashimoto, Naoko [1 ]
Mayama, Takafumi [1 ]
Koide, Hisashi [1 ]
Sasano, Hironobu [3 ]
Nakatani, Yukio [4 ]
Imamoto, Takashi [5 ]
Ichikawa, Tomohiko [5 ]
Yokote, Koutaro [1 ]
Tanaka, Tomoaki [1 ]
机构
[1] Chiba Univ, Grad Sch Med, Dept Clin Cell Biol, Chiba 2608670, Japan
[2] Toho Univ, Ctr Diabet Metab & Endocrinol, Sakura Med Ctr, Chiba 2748510, Japan
[3] Tohoku Univ, Grad Sch Med, Dept Pathol, Sendai, Miyagi 980, Japan
[4] Chiba Univ, Grad Sch Med, Dept Pathol, Chiba 2608670, Japan
[5] Chiba Univ, Grad Sch Med, Dept Urol, Chiba 2608670, Japan
关键词
INDEPENDENT CUSHINGS-SYNDROME; ABERRANT HORMONE-RECEPTORS; DROPLET DIGITAL PCR; ADRENOCORTICAL HYPERPLASIA; VASOPRESSIN; MUTATIONS; EXPRESSION; SECRETION; CORTISOL;
D O I
10.4158/EP15756.OR
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Primary macronodular adrenal hyperplasia (PMAH) is considered a predominantly sporadic disease, but familial forms are well recognized. Genetic studies revealed germline mutations in the armadillo repeat containing 5 gene (ARMC5) in the majority of PMAH cases. Furthermore, somatic ARMC5 mutations, as different types of second-hit mutations and loss of heterozygosity have been reported in each adrenal nodule in PMAH. Here, we describe the involvement of ARMC5 alteration in a familial case of PMAH. Methods: In our study, we performed clinical and genetic evaluations in a mother and her son with familial PMAH. To search for mutations and deletion of ARMC5, we used Sanger sequencing and droplet digital polymerase chain reaction (ddPCR), respectively. Results: Both patients showed the same phenotype of subclinical Cushing syndrome, with mild excess of mineralocorticoids and vasopressin-responsive cortisol secretion. The ddPCR analysis demonstrated that both mother and son had germline deletions in exons 1 to 5 of the ARMC5 gene locus. Furthermore, Sanger sequencing of DNA from the right and left adrenal nodules as well as peripheral blood of the son revealed the presence of another germline, missense mutation in ARMC5 exon 3 (p.P347S). Conclusion: This is the first report demonstrating germline deletion of ARMC5 in familial PMAH. In addition to investigating mutations, germline and somatic deletions of ARMC5 could be examined by ddPCR, which permits rapid and accurate evaluation of the ARMC5 allelic status.
引用
收藏
页码:1152 / 1160
页数:9
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