Sonic hedgehog (SHH) mutation in patients within the spectrum of holoprosencephaly.
Holoprosencephaly (HPE) is a malformation sequence where the cerebral hemispheres fail to separate into distinct left and right halves. It can be associated with midline structural anomalies of the central nervous system and/or face. SHH is the major gene implicated in HPE and it plays a critical role in early forebrain and central nervous system development. SHH is expressed in the human embryo in the notochord, the floorplate of the neural tube, and the posterior limb buds. In the present study we performed mutational analysis of the entire coding region of the SHH gene in 37 unrelated individuals with the HPE spectrum. Three different variants were found throughout the extent of the gene. No genotype-phenotype correlation is evident based on the type or position of the mutations. This study confirms the great genetic heterogeneity of the disease and the difficulty to establish genotype-phenotype correlations.
Bertolacini
Claudia Danielli Pereira
CD
Hospital de Reabilitação de Anomalias Craniofaciais, Departament of Genetics, USP/Bauru, Rua Sílvio Marchione, 3-20, Bauru, SP, Brazil.
Richieri-Costa
Antonio
A
Ribeiro-Bicudo
Lucilene Arilho
LA
D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005973:Glutamine / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics*; D006639:Histidine / Q000235:genetics; D016142:Holoprosencephaly / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009154:Mutation / Q000235:genetics*
D053823:Hedgehog Proteins; D005973:Glutamine; D006639:Histidine