Non-random distribution of mutations in the PHEX gene, and under-detected missense mutations at non-conserved residues.
Thirty newly detected mutations in the PHEX gene are reported, and pooled with all the previously published mutations. The spectrum of mutations displayed 16% deletions, 8% insertions, 34% missense, 27% nonsense, and 15% splice site mutations, with two peaks in exon 15, and 17. Since 32.8% of PHEX amino acids were conserved in the endopeptidases family, the number of missense mutations detected at non-conserved residues was smaller than expected, whereas the number of nonsense mutations observed at non-conserved residues was very close to the expected number. Compared with conserved amino acids, the changes in non-conserved amino acids may result in benign polymorphisms or possibly mild disease that may go undiagnosed.
Filisetti
D
D
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, ULP, Illkirch, France.
Ostermann
G
G
von Bredow
M
M
Strom
T
T
Filler
G
G
Ehrich
J
J
Pannetier
S
S
Garnier
J M
JM
Rowe
P
P
Francis
F
F
Julienne
A
A
Hanauer
A
A
Econs
M J
MJ
Oudet
C
C
D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D016366:Open Reading Frames; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D010641:Phenotype; D011506:Proteins / Q000235:genetics*
D011506:Proteins; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human