BACKGROUND: The major genetic cause of Currarino syndrome (CS), a congenital 
malformation syndrome typically characterized by sacral agenesis, anorectal 
malformation, and presence of a pre-sacral mass, is known to be pathogenic 
variants in motor neuron and pancreas homeobox 1 (MNX1), which exist in almost 
all familial cases and 30% of sporadic cases. Less commonly, a large deletion or 
a complex rearrangement involving the 7q36 region is associated with CS. We 
investigated the spectrum of MNX1 pathogenic variants and associated clinical 
features in the Korean patients with CS.
METHODS: We enrolled 25 patients with CS, including 24 sporadic cases and one 
familial case. Direct sequencing of MNX1 and multiplex ligation-dependent probe 
amplification were performed. We also analyzed clinical phenotypes and evaluated 
genotype-phenotype correlations.
RESULTS: We identified six novel variants amongst a total of six null variants, 
one missense variant, and one large deletion. The null variants included four 
frameshift variants (p.Gly98Alafs* 124, p.Gly145Alafs*77, p.Gly151Leufs*67, and 
p.Ala216Profs*5) and two nonsense variants (p.Tyr186* and p.Gln212*). The 
missense variant, p.Lys295Gln, was located in the highly-conserved homeobox 
domain and was predicted to be deleterious. A large deletion involving the 7q36 
region was detected in one patient. Pathogenic variants in MNX1 were detected in 
28% of all CS cases and 25% of sporadic cases. The clinical phenotype was 
variable in patients with and without pathogenic variants; no significant 
genotype-phenotype correlation was observed.
CONCLUSIONS: This study revealed the spectrum and phenotypic variability of MNX1 
pathogenic variants in the Korean population.