Research on costello syndrome reported by scientists at Haukeland University
2007 OCT 9 -- "Mutations in genes involved in Ras signalling cause Noonan syndrome and other disorders characterised by growth disturbances and variable neuro-cardio-facio-cutaneous features. We describe two sisters, 46 and 31 years old, who presented with dysmorphic features, hypotonia, feeding difficulties, retarded growth and psychomotor retardation early in life," investigators in Bergen, Norway report. "The patients were initially diagnosed with Costello syndrome, and autosomal recessive inheritance was assumed. Remarkably, however, we identified a germline HRAS mutation (G12A) in one sister and a germline KRAS mutation (F156L) in her sibling. Both mutations had arisen de novo. The F156L mutant K-Ras protein accumulated in the active, guanosine triphosphate-bound conformation and affected downstream signalling. The patient harbouring this mutation was followed for three decades, and her cardiac hypertrophy gradually normalised. However, she developed severe epilepsy with hippocampal sclerosis and atrophy," wrote O. Sovik and colleagues, Haukeland University. The researchers concluded: "The occurrence of distinct de novo mutations adds to variable expressivity and gonadal mosaicism as possible explanations of how an autosomal dominant disease may manifest as an apparently recessive condition." Sovik and colleagues published their study in the Journal of Medical Genetics (De novo HRAS and KRAS mutations in two siblings with short stature and neuro-cardio-facio-cutaneous features. Journal of Medical Genetics, 2007;44(7):E84). For additional information, contact A. Molven, University of Bergen, Haukeland University Hospital, Gade Institute, Sect Pathology, N-5021 Bergen, Norway. The publisher of the Journal of Medical Genetics can be contacted at: B M J Publishing Group, British Med Association House, Tavistock Square, London WC1H 9JR, England. Keywords: Norway, Bergen, Costello Syndrome, Genetics, Noonan Syndrome, Haukeland University. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.
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