Mutational analysis of SHH and GLI3 in anorectal malformations.
BACKGROUND
Anorectal malformations (congenital absence of the anal opening) are among the most common pediatric surgical problems and carry a significant chronic morbidity.


METHODS
Direct sequencing was used to screen 88 anorectal malformations patients for mutations and polymorphisms in SHH and GLI3. These genes were chosen according to the phenotype presented by mutant mice and their expression patterns.


RESULTS
We report on 10 GLI3 variants (IVS3+141C>G, T183A, IVS4+124T>C, IVS7+17G>A, IVS8+1 G>C, N503N, P941P, P998L, A1005A, A1039A) and four SHH mutation/variants (IVS1-49C>T, IVS2+111A>C, L214L, G290D).


CONCLUSIONS
These variants are not over-represented in the healthy population and most are predicted to be benign. This study conveys the problematic assessment of the pathogenic role in disease of rare point mutations and variants.
Garcia-Barceló
Maria-Mercè
MM
Department of Surgery, University of Hong Kong, Hong Kong SAR, China.
Chi-Hang Lui
Vincent
V
Miao
Xiaoping
X
So
Man-ting
MT
Yuk-yu Leon
Thomas
T
Yuan
Zhen-wei
ZW
Li
Long
L
Liu
Lei
L
Wang
Bin
B
Sun
Xiao-bing
XB
Huang
Liu-Ming
LM
Tou
Jin-fa
JF
Sau-wai Ngan
Elly
E
Cherny
Stacey S
SS
Chan
Kin-wai
KW
Lee
Kim-hung
KH
Wang
Weiling
W
Kak-yuen Wong
Kenneth
K
Kwong-hang Tam
Paul
P
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D001003:Anal Canal / Q000002:abnormalities*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011237:Predictive Value of Tests; D012007:Rectum / Q000002:abnormalities*; D013577:Syndrome; D000074290:Zinc Finger Protein Gli3
C065683:GLI3 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C509239:SHH protein, human; D000074290:Zinc Finger Protein Gli3