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- Title
Spectrum of MNX1 Pathogenic Variants and Associated Clinical Features in Korean Patients with Currarino Syndrome.
- Authors
Seungjun Lee; 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
- 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.
- Subjects
CURRARINO syndrome; HUMAN abnormality genetics; CAUDAL regression syndrome; HOMEOBOX genes; HUMAN genetic variation
- Publication
Annals of Laboratory Medicine, 2018, Vol 38, Issue 3, p242
- ISSN
2234-3806
- Publication type
Article
- DOI
10.3343/alm.2018.38.3.242