Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia.
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.
De Filippi
Paola
P
Medical Genetics, Department of Human and Hereditary Pathology, University of Pavia, Pavia, Italy.
Zecca
Marco
M
Lisini
Daniela
D
Rosti
Vittorio
V
Cagioni
Claudia
C
Carlo-Stella
Carmelo
C
Radi
Orietta
O
Veggiotti
Pierangelo
P
Mastronuzzi
Angela
A
Acquaviva
Antonio
A
D'Ambrosio
Alfonso
A
Locatelli
Franco
F
Danesino
Cesare
C
D002478:Cells, Cultured; D019066:Facies; D005347:Fibroblasts / Q000378:metabolism; D011905:Genes, ras / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics*; D008297:Male