Pallister-Hall syndrome: unreported skeletal features of a GLI3 mutation.
We describe two patients with Pallister-Hall syndrome (PHS), both with evidence of a generalized skeletal dysplasia as typified by upper and lower acromesomelic limb shortening and the previously unreported fibular hypoplasia, radio-ulnar bowing, and proximal epiphyseal hypoplasia. Genomic DNA was only available for sequencing analysis in patient 2 and the mutation, c.3386_3387delTT was detected in exon 14 of the GL13 gene. It is also possible that the findings in patient 1 represent the phenotypic expression of a novel GLI3 mutation. This report further expands the PHS phenotype and raises the possibility of specific GLI3 mutations resulting in more severe skeletal features. It also suggests that PHS should be included in the differential diagnosis of antenatally ascertained acromesomelic limb shortening and bowing with fibular hypoplasia particularly in the presence of polysyndactyly.
Roscioli
T
T
South Eastern Sydney Genetics Service, Sydney Children's Hospital, Sydney, Australia.
Kennedy
D
D
Cui
J
J
Fonseca
B
B
Watson
G F
GF
Pereira
J
J
Xie
Y-G
YG
Mowat
D
D
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000025:Abortion, Eugenic; D001483:Base Sequence; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D017809:Fatal Outcome; D005333:Fetus; D005360:Fibula / Q000002:abnormalities*; D006222:Hamartoma / Q000473:pathology; D006801:Humans; D007027:Hypothalamic Diseases / Q000473:pathology; D051741:Kruppel-Like Transcription Factors; D017880:Limb Deformities, Congenital / Q000473:pathology*; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*; D000074290:Zinc Finger Protein Gli3
D004268:DNA-Binding Proteins; C065683:GLI3 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3; D004247:DNA