Null phenotype of neurofibromatosis type 1 in a carrier of a heterozygous atypical NF1 deletion due to mosaicism.

Autor: Kluwe L; Department of Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Friedrich RE; Department of Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Farschtschi SC; Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Hagel C; Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kehrer-Sawatzki H; Institute of Human Genetics, University Hospital Ulm, Ulm, Germany., Mautner VF; Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2020 Jul; Vol. 41 (7), pp. 1226-1231. Date of Electronic Publication: 2020 Apr 13.
DOI: 10.1002/humu.24022
Abstrakt: We coincidently detected an atypical deletion of at least 1.3-Mb, encompassing the NF1 tumor suppressor gene and several adjacent genes at an apparent heterozygous level in the blood of a 65-year-old female patient. She had multiple subcutaneous tumors that appeared with a certain similarity of subcutaneous neurofibromas, which, however, was revealed as lipomas by histological examination. Comprehensive and exhaustive clinical and radiological examinations did not detect any neurofibromatosis type 1-related clinical symptoms in the patient. Multiplex ligation-dependent probe amplification detected no or only very low level of the 1.3-Mb NF1 deletion in six lipomas and two skin biopsies. Digital polymerase chain reaction estimated the proportion of cells carrying a heterozygous NF1 deletion at 87% in the blood, and 8%, 10%, 13%, 17%, and 20%, respectively, in the five lipomas investigated by this method, confirming our hypothesis of mosaicism. Our findings suggest that de novo cases of genetic disease are potentially mosaic regardless of finding the mutation at an apparently heterozygous level in the blood and that the possibility of mosaicism should be considered in genotype-phenotype studies and genetic counseling.
(© 2020 The Authors. Human Mutation Published by Wiley Periodicals, Inc.)
Databáze: MEDLINE
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