Neurofibromatosis type 1 in two siblings due to maternal germline mosaicism. (27th May 2013)

• Record Type: Journal Article
• Authors: Trevisson, E.; Forzan, M.; Salviati, L.; Clementi, M.
• Is Part Of: Clinical genetics. Volume 85:Number 4(2014:Apr.)
• Page Start: 386
• Page End: 389
• Publication Date: 2013-05-27
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12177
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Neurofibromatosis type 1 (NF1) is caused by loss of function mutations of the <italic>NF1</italic> gene, which are <italic>de novo</italic> in 50% of cases. Although this gene shows one of the highest mutation rates in the human genome, germline mosaicism is very rare in this condition. We describe the molecular analysis of a family in which neurofibromatosis type 1 occurred in two out of four siblings born to unaffected parents. Molecular analysis of the <italic>NF1</italic> gene identified in both patients the same splicing mutation c.1392+1G&gt;A, which was absent in parental lymphocytes. Microsatellite analysis showed that the two affected siblings shared the same maternal allele, however a specific PCR‐RFLP assay excluded the presence of the <italic>NF1</italic> splicing mutation in multiple maternal tissues. Our molecular and clinical findings are consistent with a germline mosaicism for the <italic>NF1</italic> splicing mutation. This is the first case of maternal germline mosaicism for a <italic>NF1</italic> mutation characterized so far at the molecular level. Our data confirm that germline mosaicism is rare in neurofibromatosis 1, but it has important implications for genetic counseling.</p> </abstract>