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.
Medical Genetics, Department of Human and Hereditary Pathology, University of Pavia, Pavia, Italy.
Paola
P
De Filippi
Marco
M
Zecca
Daniela
D
Lisini
Vittorio
V
Rosti
Claudia
C
Cagioni
Carmelo
C
Carlo-Stella
Orietta
O
Radi
Pierangelo
P
Veggiotti
Angela
A
Mastronuzzi
Antonio
A
Acquaviva
Alfonso
A
D'Ambrosio
Franco
F
Locatelli
Cesare
C
Danesino
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