Acquired uniparental disomy of chromosome 7 in a patient with mirage syndrome that veiled a pathogenic samd9 variant

Kanako Tanase-Nakao, Masanobu Kawai, Kazuko Wada, Masayo Kagami, Satoshi Narumi

Research output: Contribution to journalArticlepeer-review


Gain-of-function variants in SAMD9, which resides on chromosome 7, cause MIRAGE syndrome that is associated with congenital adrenal insufficiency and gonadal dysgenesis. We previously reported a Japanese patient with MIRAGE syndrome carrying a de novo heterozygous SAMD9 variant (p.Ala1479Ser). In this study, we confirmed the pathogenicity of Ala1479Ser-SAMD9 in vitro. Genetic study results revealed an atypically low variant allele frequency (26%) and we suspected of genomic rearrangement(s) involving chromosome 7. Single nucleotide polymorphism (SNP) array and short tandem repeat analysis showed presence of mosaic maternal isodisomic uniparental disomy 7 (UPD7). Deep sequencing using DNA samples obtained at 0, 6, 10, and 25 mo of age revealed that the percentage of cells with UPD7 increased constantly from 6% to 82% over 25 mo, and this increase coincided with a decrease in the percentage of cells with p.Ala1479Ser from 94% to nearly undetectable levels. We further screened for low-allele-frequency and rare SAMD9 variants in eight patients with Silver-Russel syndrome and maternal UPD7; however, none of the patients harbored such a variant. In conclusion, our case demonstrates that genetic findings can vary considerably in patients with MIRAGE syndrome and that a comprehensive diagnostic approach, including SNP array and deep sequencing, is important in such cases.

Original languageEnglish
Pages (from-to)163-169
Number of pages7
Journalclinical pediatric endocrinology
Issue number4
Publication statusPublished - 2021 Oct
Externally publishedYes


  • MIRAGE syndrome
  • Silver-Russell syndrome
  • Uniparental disomy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


Dive into the research topics of 'Acquired uniparental disomy of chromosome 7 in a patient with mirage syndrome that veiled a pathogenic samd9 variant'. Together they form a unique fingerprint.

Cite this