Joan N R Kromosoeto

Publications (2)6.69 Total impact

• Article: A clinical and genetic overview of 18 years Neurofibromatosis type 1 molecular diagnostics in the Netherlands.

  Rick van Minkelen, Yolande van Bever, Joan N R Kromosoeto, Caroline J Withagen-Hermans, Anja Nieuwlaat, Dicky J J Halley, Ans M W van den Ouweland
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  ABSTRACT: NF1 mutations are the underlying cause of Neurofibromatosis type 1 (NF1), a neuro-cardio-facio-cutaneous syndrome (NCFC). Because of the clinical overlap between NCFCs, genetic analysis of NF1 is necessary to confirm a clinical diagnosis NF1. The present report describes the clinical and genetic findings of 18 years of NF1 molecular diagnostics in the Netherlands. A pathogenic mutation was found in 59.3% (1178/1985) of the index patients, mostly de novo (73.8%). The majority of the index patients (64.3%) fulfilled the NIH NF1 criteria, a pathogenic mutation was found in 80.9% of these patients. Seventy-four percent of the index patients with an NF1 pathogenic mutation and not fulfilling the NF1 criteria is <12yr, in agreement with the fact that some NF1 symptoms appear after puberty. Genotype-phenotype correlations were studied for 527 index patients. NF1 patients with a type 1 microdeletion have a 6-fold higher risk of special education versus NF1 patients with an intragenic mutation. No evidently milder NF1 phenotype for patients with a missense mutation was observed. Forty-six prenatal analyses were performed in 28 (2.4%) families, of which 29 (63%) showed heterozygosity for the familial pathogenic mutation. This indicates that there is a need for prenatal NF1 testing.
  Clinical Genetics 05/2013; · 3.13 Impact Factor
• Source

  Available from: Dicky Halley

  Article: Multiplex ligation-depending probe amplification is not suitable for detection of low-grade mosaicism.

  Monique M van Veghel-Plandsoen, Cokkie H Wouters, Joan N R Kromosoeto, Mariska C den Ridder-Klünnen, Dicky J J Halley, Ans M W van den Ouweland
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  ABSTRACT: 'Apparent non-penetrance' occurs in several genetic disorders, including tuberous sclerosis complex and neurofibromatosis type 1: clinically unaffected parents may have multiple affected offspring. Germ line or somatic mosaicism in one of the parents of the index patient is the probable cause and results in an enhanced recurrence risk. Therefore, it is of great importance to use the most sensitive technology for testing DNA of the parents of the index patient for the presence/absence of the familial mutation. To detect large rearrangements multiplex ligation-depending probe amplification (MLPA) is often used. Here we show that MLPA is less sensitive in detecting low-grade somatic mosaicism than fluorescence in situ hybridization (FISH) or a mutation-specific PCR test. Therefore, we recommend FISH (if possible) or PCR analysis for the analysis of parental DNA.
  European journal of human genetics: EJHG 04/2011; 19(9):1009-12. · 3.56 Impact Factor