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First evidence of genotype-phenotype correlations in Gorlin syndrome
Ist Teil von
Journal of medical genetics, 2017-08, Vol.54 (8), p.530
Ort / Verlag
England
Erscheinungsjahr
2017
Link zum Volltext
Beschreibungen/Notizen
Gorlin syndrome (GS) is an autosomal dominant syndrome characterised by multiple basal cell carcinomas (BCCs) and an increased risk of jaw cysts and early childhood medulloblastoma. Heterozygous germline variants in
and
encoding components of the Sonic hedgehog pathway explain the majority of cases. Here, we aimed to delineate genotype-phenotype correlations in GS.
We assessed genetic and phenotypic data for 182 individuals meeting the diagnostic criteria for GS (median age: 47.1; IQR: 31.1-61.1). A total of 126 patients had a heterozygous pathogenic variant, 9 had
pathogenic variants and 46 had no identified mutation.
Patients with variants were more likely to be diagnosed earlier (p=0.02), have jaw cysts (p=0.002) and have bifid ribs (p=0.003) or any skeletal abnormality (p=0.003) than patients with no identified mutation. Patients with a missense variant in
were diagnosed later (p=0.03) and were less likely to develop at least 10 BCCs and jaw cysts than those with other pathogenic
variants (p=0.03). Patients with
pathogenic variants were significantly more likely than those with
pathogenic variants to develop a medulloblastoma (p=0.009), a meningioma (p=0.02) or an ovarian fibroma (p=0.015), but were less likely to develop a jaw cyst (p=0.0004).
We propose that the clinical heterogeneity of GS can in part be explained by the underlying or
variant.