Spectrum of<i>MNX1</i>Pathogenic Variants and Associated Clinical Features in Korean Patients with Currarino Syndrome

Lee, Seungjun; Kim, Eun Jin; Cho, Sung Im; Park, Hyun Woong; Seo, Soo Hyun; Seong, Moon Woo; Park, Sung Sup; Jung, Sung Eun; Lee, Seong Cheol; Park, Kwi Won; Kim, Ho

doi:10.3343/alm.2018.38.3.242

Cited by 8 publications

(5 citation statements)

References 37 publications

(88 reference statements)

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“…Consistent with possible sex-biased expression of MNX1 some reports from China and Korea of Currarino syndrome, which is caused by dominant MNX1 mutations different from those that cause NDM, reported higher disease detection among females 29 .…”

Section: Literature Review and Discussionsupporting

confidence: 59%

MNX1 mutations causing neonatal diabetes: Review of the literature and report of a case with extra‐pancreatic congenital defects presenting in severe diabetic ketoacidosis

Aly

Franco

Flanagan

et al. 2022

J of Diabetes Invest

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The MNX1 gene encodes a homeobox transcription factor found to be important for pancreatic beta cell differentiation and development. Mutations of the MNX1 gene that cause permanent neonatal diabetes mellitus (PNDM) are rare and have been reported in only two cases. Both cases presented with hyperglycemia, with one case having isolated PNDM while the other had PNDM and multiple neurologic, skeletal, lung, and urologic congenital anomalies resulting in death in early infancy. We describe the genetic and clinical features of a preterm male infant with a homozygous [c.816C > A p.(Phe272Leu)] MNX1 mutation. Our proband is the first case to present in severe diabetic ketoacidosis (DKA), indicating severe insulin deficiency. Unlike the previously reported female case who had the same mutation and presented with isolated PNDM, our proband had hypospadias and congenital umbilical hernia and showed poor growth on follow up. Our case suggests that MNX1 mutations causing NDM can result in a range of extra‐pancreatic features and a variable phenotype, similar to other transcription factors causing NDM such as GATA6 and GATA4 mutations. We also cannot exclude the possibility of sex‐biased expression of MNX1 gene (which was recently reported for other monogenic/neonatal diabetes genes such as the NEUROD1 and HNF4A in humans) since the two male cases had associated multiple anomalies while the female case had isolated PNDM. Our report further defines the phenotype caused by recessive homozygous MNX1 mutations and explores potential new mechanisms regulating MNX1 gene expression which should be further explored.

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Section: Literature Review and Discussionsupporting

confidence: 59%

MNX1 mutations causing neonatal diabetes: Review of the literature and report of a case with extra‐pancreatic congenital defects presenting in severe diabetic ketoacidosis

Aly

Franco

Flanagan

et al. 2022

J of Diabetes Invest

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“…Twenty-three patients (72%) in our series had an MNX1 mutation. There is no obvious genotypephenotype correlation; however, individuals with genetic mutations often have more severe phenotypes (9,10). For complete CS, whether there is MNX1 mutation or not, the evaluation should be performed by radiologic examinations.…”

Section: Discussionmentioning

confidence: 99%

Characterization of complete Currarino syndrome in pediatrics—a comparison between CT and MRI

Chen¹,

Zheng²,

Wang³

et al. 2022

Ann Transl Med

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Background: This study sought to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of the classical triad elements and the associated anomalies in pediatric complete Currarino syndrome (CS) to evaluate the advantages and disadvantages of the 2 different imaging methods in displaying the abnormalities of this disease. Methods:The clinical and radiological features of 32 pediatric patients with complete CS diagnosed histologically and/or radiologically were retrospectively analyzed.Results: All 32 complete CS patients presented with the classical triad of congenital anorectal malformation (ARM), sacral agenesis, and presacral mass. Anal atresia, which is the most common congenital ARM, was observed in 19 of the 32 patients (59.4%). Sacral agenesis was mainly type IV (75%). Among the presacral masses, true tumors and pseudotumors accounted for about half each. All of the 15 true tumors were presacral teratomas. 25 patients had associated anomalies, including tethered cord, filum lipoma, and hydronephrosis. 24 patients underwent both CT and MRI examinations. While CT was better than MRI in displaying sacral anomaly (P<0.05), MRI was more sensitive than CT at detecting presacral mass, spinal dysraphism, and congenital anal atresia (P<0.05).Conclusions: CT and MRI have different efficiencies at displaying the abnormalities of the complete CS.As a non-invasive method, MRI has significant advantages in diagnosing complete CS, especially in revealing the details of ARM, presacral mass, and associated spinal dysraphism.

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“…The Human Gene Mutation Database and ClinVar database were screened for previously reported variants. For in silico prediction, SIFT, Mutation Taster and PolyPhen2 were used as described previously 35 . Variants were classified as benign, likely benign, VUS, likely pathogenic and pathogenic, according to the ACMG/AMP guidelines 16 .…”

Section: Methodsmentioning

confidence: 99%

Clinical and genetic profiling of nevoid basal cell carcinoma syndrome in Korean patients by whole-exome sequencing

Kim

Hur

et al. 2021

Sci Rep

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Nevoid basal cell carcinoma syndrome (NBCCS) is mainly characterised by multiple basal cell carcinomas (BCCs) caused by PTCH1, PTCH2, and SUFU. However, clinical and genetic data on Asian NBCCS patients are limited. We aimed to analyse the clinical phenotypes and genetic spectrum of Korean patients with NBCCS. Fifteen patients with NBCCS at Seoul National University Hospital were included, and their clinical data were analysed. Whole-exome sequencing and/or multiplex ligation-dependent probe amplification using peripheral blood were performed to identify genetic causes. Genetic analysis revealed that 73.3% (11/15) of the patients carried 9 pathogenic variants, only in the PTCH1 gene. Variants of uncertain significance (VUS) and likely benign were also detected in 2 (13.3%) and 2 (13.3%) patients, respectively. BCCs were found in the majority of the cases (93.3%) and the number of BCCs increased with age (ρ = 0.595, P = 0.019). This study revealed that PTCH1 pathogenic variants were the main cause of NBCCS in Korean patients. As BCCs are commonly detected, a periodic dermatologic examination is recommended. Finally, our results support the addition of genetic screening to the existing criteria for NBCCS diagnosis.

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Spectrum ofMNX1Pathogenic Variants and Associated Clinical Features in Korean Patients with Currarino Syndrome

Cited by 8 publications

References 37 publications

MNX1 mutations causing neonatal diabetes: Review of the literature and report of a case with extra‐pancreatic congenital defects presenting in severe diabetic ketoacidosis

MNX1 mutations causing neonatal diabetes: Review of the literature and report of a case with extra‐pancreatic congenital defects presenting in severe diabetic ketoacidosis

Characterization of complete Currarino syndrome in pediatrics—a comparison between CT and MRI

Clinical and genetic profiling of nevoid basal cell carcinoma syndrome in Korean patients by whole-exome sequencing

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