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Normal Immune Function in a Newborn With Early Identification of a SAMD9 Mutation Presenting With Growth Restriction, Thrombocytopenia, and Primary Adrenal Insufficiency

Year: 2025

Type: article

Abstract: MIRAGE syndrome is a multi-organ disease caused by gain-of-function (GOF) mutations in the viral restriction factor SAMD9. Herein, we present the case of a 32-week pre-term female neonate with severe intrauterine growth restriction, primary adrenal insufficiency, and persistent thrombocytopenia. A rapid trio-whole exome sequencing at 23-days of age found a de novo SAMD9 G1048R mutation, consistent with a diagnosis of MIRAGE syndrome, and at this time was not found to have evidence of immune abnormalities or hematologic malignancy. Analysis of predicted tertiary structures from our patient's SAMD9 G1048R mutation demonstrated structural similarities to known SAMD9 GOF variants. Absence of immunologic and oncologic manifestations in this patient may relate to early identification and reflect low SAMD9 expression during the neonatal window. Risk for developing immune deficiency and malignancy may continue to increase as this patient grows older, thus requiring close outpatient surveillance to mitigate future risk of these complications.

Source: Clinical Case Reports

DOI: 10.1002/ccr3.71453