MNX1 (HLXB9) mutations in Currarino patients.
OBJECTIVE
The combination of partial absence of the sacrum, anorectal anomalies, and presacral mass constitutes Currarino syndrome (CS), which is associated with mutations in MNX1 motor neuron and pancreas homeobox 1 (previously HLXB9). Here, we report on the MNX1 mutations found in a family segregating CS and in 3 sporadic CS patients, as well as on the clinical characteristics of the affected individuals.


METHODS
MNX1 mutations were identified by direct sequencing the coding regions, intron/exon boundaries of MNX1 in 5 CS Japanese family members and 3 Chinese sporadic cases and their parents.


RESULTS
There were 2 novel (P18PfsX37, R243W) and 2 previously described (W288G and IVS2 + 1G > A) mutations. These mutations were not found in 198 control individuals and are predicted to impair the functioning of the MNX1 protein.


CONCLUSIONS
The variability of the CS phenotype among related or unrelated patients bearing the same mutation advocates for differences in the genetic background of each individual and invokes the implication of additional CS susceptibility genes.
Garcia-Barceló
Maria-Mercè
MM
Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Lui
Vincent Chi-Hang
VC
So
Man-ting
MT
Miao
Xiaoping
X
Leon
Thomas Yuk-yu
TY
Yuan
Zhen-wei
ZW
Ngan
Elly Sau-wai
ES
Ehsan
Toufique
T
Chung
Patrick Ho-yu
PH
Khong
Pek-lan
PL
Wong
Kenneth Kak-yuen
KK
Tam
Paul Kwong-hang
PK
D000015:Abnormalities, Multiple / Q000235:genetics*; D001003:Anal Canal / Q000002:abnormalities*; D044466:Asian People / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D012447:Sacrum / Q000002:abnormalities*; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
D018398:Homeodomain Proteins; C490003:MNX1 protein, human; D014157:Transcription Factors; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human