Mol Genet Genomic Med

. 2023 Jan 25;e2139.

 doi: 10.1002/mgg3.2139. Online ahead of print. https://pubmed.ncbi.nlm.nih.gov/36695166/

Two sisters with cardiac-urogenital syndrome secondary to pathogenic splicing variant in the MYRF gene with unaffected parents: A case of gonadal mosaicism?

Katerina Slaba ¹, Marta Jezova ², Petra Pokorna ³, Hana Palova ³, Jana Tuckova ¹, Jan Papez ¹, Dagmar Prochazkova ^1 4, Petr Jabandziev ^1 2, Ondrej Slaby ^3 5

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• PMID: 36695166
• DOI: 10.1002/mgg3.2139

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Abstract

Background: Cardiac-urogenital syndrome [MIM # 618280] is a newly described very rare syndrome associated with pathogenic variants in the myelin regulatory factor (MYRF) gene that leads to loss of protein function. MYRF is a transcription factor previously associated only with the control of myelin-related gene expression. However, it is also highly expressed in other tissues and associated with various organ anomalies. The clinical picture is primarily dominated by complex congenital cardiac developmental defects, pulmonary hypoplasia, congenital diaphragmatic hernia, and urogenital malformations.

Case presentation: We present case reports of two siblings of unrelated parents in whom whole-exome sequencing was indicated due to familial occurrence of extensive developmental defects. A new, previously undescribed splicing pathogenic variant c.1388+2T>G in the MYRF gene has been identified in both patients. Both parents are unaffected, tested negative, and have another healthy daughter. The identical de novo event in siblings suggests gonadal mosaicism, which can mimic recessive inheritance.

Conclusions: To our knowledge, this is the first published case of familial cardiac-urogenital syndrome indicating gonadal mosaicism.

Keywords: MYRF gene; Scimitar syndrome; cardiac-urogenital syndrome; familiar occurrence; whole-exome sequencing.

© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC