Format

Send to

Choose Destination
Ann Lab Med. 2018 May;38(3):242-248. doi: 10.3343/alm.2018.38.3.242.

Spectrum of MNX1 Pathogenic Variants and Associated Clinical Features in Korean Patients with Currarino Syndrome.

Author information

1
Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
2
Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
3
Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
4
Department of Laboratory Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea.
5
Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
6
Department of Pediatric Surgery, Seoul National University College of Medicine, Seoul, Korea.
7
Department of Pediatric Surgery, Seoul National University College of Medicine, Seoul, Korea. spkhy02@snu.ac.kr.

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.

KEYWORDS:

Currarino syndrome; Korean; MNX1; Pathogenic variant

PMID:
29401559
PMCID:
PMC5820069
DOI:
10.3343/alm.2018.38.3.242
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for The Korean Society for Laboratory Medicine Icon for PubMed Central
Loading ...
Support Center