title: GERMLINE DELETION OF ARMC5 IN FAMILIAL PRIMARY MACRONODULAR ADRENAL HYPERPLASIA.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.forename: Sawako
authors.initials: S
authors.lastname: Suzuki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
authors.forename: Emi
authors.initials: E
authors.lastname: Oohara
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Nakayama
authors.forename: Eri
authors.initials: E
authors.lastname: Komai
authors.forename: Akina
authors.initials: A
authors.lastname: Shiga
authors.forename: Takashi
authors.initials: T
authors.lastname: Kono
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takiguchi
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Higuchi
authors.forename: Ikki
authors.initials: I
authors.lastname: Sakuma
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Nagano
authors.forename: Naoko
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Takafumi
authors.initials: T
authors.lastname: Mayama
authors.forename: Hisashi
authors.initials: H
authors.lastname: Koide
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Takashi
authors.initials: T
authors.lastname: Imamoto
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics* / Q000473:pathology; D000369:Aged, 80 and over; D051186:Armadillo Domain Proteins; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009035:Mothers; D009679:Nuclear Family; D010375:Pedigree; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C000590373:ARMC5 protein, human; D051186:Armadillo Domain Proteins; D025521:Tumor Suppressor Proteins