Germ‐line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia

• Published in: British journal of haematology Vol. 147; no. 5; pp. 706 - 709
• Main Authors: De Filippi, Paola, Zecca, Marco, Lisini, Daniela, Rosti, Vittorio, Cagioni, Claudia, Carlo‐Stella, Carmelo, Radi, Orietta, Veggiotti, Pierangelo, Mastronuzzi, Angela, Acquaviva, Antonio, D’Ambrosio, Alfonso, Locatelli, Franco, Danesino, Cesare
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2009; Blackwell
• Subjects: Biological and medical sciences; Cells, Cultured; Facies; Fibroblasts - metabolism; Genes, ras - genetics; Genetic Predisposition to Disease; Germ-Line Mutation; Hematologic and hematopoietic diseases; Humans; Infant; JMML; Leukemia, Myelomonocytic, Juvenile - genetics; Male; Medical sciences; Noonan; PTPN11; RAS; JMML; PTPN11 gene; Hematology; RAS; Noonan; PTPN11; C-Onc gene; Germ line; Genetics; Juvenile myelomonocytic leukemia; Mutation; Ras gene; Protooncogene
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/j.1365-2141.2009.07894.x

Summary We report the case of a child with clinical and haematological features indicative of juvenile myelomonocytic leukaemia (JMML). The patient showed dysmorphic features: high forehead, bilateral epicanthal folds, long eyebrows, low nasal bridge and slightly low‐set ears. A 38G>A (G13D) mutation in exon 1 of the NRAS gene was first demonstrated on peripheral blood cells, and then confirmed on granulocyte‐macrophage colony‐forming units. The same mutation was also found in buccal swab, hair bulbs, endothelial cells, skin fibroblasts. This case suggests for the first time that constitutional mutations of NRAS may be responsible for development of a myeloproliferative/myelodysplastic disorder in children.