Expanding mutational spectrum of HRAS by a patient with Schimmelpenning–Feuerstein–Mims syndrome
Qi Luo, Qin Zhang, and Jinwen Shen contributed equally to the manuscript.
Abstract
As one of the epidermal nevus syndromes, Schimmelpenning–Feuerstein–Mims (SFM) is characterized by craniofacial nevus sebaceous (NS) and extracutaneous abnormalities (e.g., brain, eyes, and bone). Here, we report a case of a 4-year-old boy who presented with significant skin abnormalities (NS in the scalp, extensive epidermal nevus along Blaschko’s lines), ocular abnormalities (strabismus), central nervous system abnormalities (seizure and mental retardation), lymphatic dysplasia (chylous pleural and pericardial effusion), cardiac abnormalities (patent foramen ovale), urogenital system abnormalities (cryptorchidism, hypospadias), and a tumor predisposition (embryonal rhabdomyosarcoma). DNA samples from NS, rhabdomyosarcoma, and peripheral blood leukocytes were analyzed by next-generation sequencing. A novel mutation in the HRAS gene (c.38G>T; p.Gly13Val) was detected in a mosaic state in NS, rhabdomyosarcoma, and peripheral blood leukocytes, with different ratio of heterozygous mutation (HRAS c.38G>T) of 39.90% (9412/23 588 reads), 73.03% (205 562/281 468 reads), and 14.16% (15 837/111 842 reads), respectively. By predicting the impact of the mutation on the biological function of protein, we found that the novel HRAS mutation (c.38G>T; p.Gly13Val) had the highest damaging scores among other HRAS mutations reported so far. This is the first reported SFM syndrome patient with novel mosaic HRAS mutation, which may help to expand the mutational spectrum of HRAS and better understand the role of HRAS in the disease.
CONFLICT OF INTEREST
None declared.
