Spectrum of MNX1 Pathogenic Variants and Associated Clinical Features in Korean Patients with Currarino Syndrome.
10.3343/alm.2018.38.3.242
- Author:
Seungjun LEE
1
;
Eun Jin KIM
;
Sung Im CHO
;
Hyunwoong PARK
;
Soo Hyun SEO
;
Moon Woo SEONG
;
Sung Sup PARK
;
Sung Eun JUNG
;
Seong Cheol LEE
;
Kwi Won PARK
;
Hyun Young KIM
Author Information
1. Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Currarino syndrome;
MNX1;
Pathogenic variant;
Korean
- MeSH:
Genes, Homeobox;
Genetic Association Studies;
Humans;
Motor Neurons;
Multiplex Polymerase Chain Reaction;
Pancreas;
Phenotype
- From:Annals of Laboratory Medicine
2018;38(3):242-248
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
