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GENATLAS PHENOTYPE
last update : 01-09-2010
Symbol NF1DEL
Location 17q11.2
Name neurofibromatosis type 1 (see NF1) caused by microdeletions in 17q11.2
Other name(s) NF1 microdeletion syndrome
Corresponding gene NF1 , RNF135 , SUZ12
Other symbol(s) DEL17Q11
Main clinical features
  • early and severe manifestation of NF1 signs, that is, development of neurofibroma and increased risk of malignancy
  • coarse face with broad nasal bridge, downslanting palpebral fissures, large nose, small/pointed chin, large ears with thick helices and macrocephaly
  • learning disability or mental retardation,
  • chilhood overgrowth and accelerated carpal bone age (Weaver-like phenotype)
  • Genetic determination chromosomal
    genomic disorder
    Prevalence microdeletion present in about 5 percent of NF1 cases
    Related entries NF1
    Function/system disorder dermatology
    neoplasia
    mental retardation
    Type MCA/MR
    Gene product
    Name contiguous gene deletion, encompassing 14 genes for type I deletion, including NF1; overgrowth is attributed to the RNF135 gene haploinsufficiency
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
      deletion haploinsufficiency the most common (type I) is 1,4 Mb in size with breakpoints located within low-copy repeats (NF1-REPs)
      deletion haploinsufficiency the less frequent (type II) is 1,2Mb between the SUZ12 gene and its pseudogene,and occurs mitotically, with somatic mosaicism and a marked female preponderance
      deletion haploinsufficiency atypical NF1 deletions
      deletion   a third type of recurrent NF1 microdeletion mediated by NAHR between LRRC37B-containing low-copy repeats PMID: 20506354
    Remark(s) genomic disorder resulting from unequal homologous recombination either meiotic (type I) or mitotic (type II)
    Genotype/Phenotype correlations because of somatic mosaicism, patients with type 2 deletions frequently exhibit milder manifestations of NF1; Type-1 NF1 deletions were found to be disproportionately associated with facial dysmorphic features (90% of patients), tall stature (46%), large hands and feet (46%), scoliosis (43%), joint hyperflexibility (72%), delayed cognitive development and/or learning disabilities (93%) and mental retardation (IQ<70; 38%), as compared with the general NF1 patient population. Significantly increased frequencies (relative to the general NF1 population) of plexiform neurofibromas (76%), subcutaneous neurofibromas (76%), spinal neurofibromas (64%) and MPNSTs (21%) were also noted in the type-1 deletion patients. Further, 50% of the adult patients exhibited a very high burden of cutaneous neurofibromas (N1000) (PMID: 20543202))