Mutation analysis of the motor neuron and pancreas homeobox 1 (MNX1, former HLXB9) gene in Swedish patients with Currarino syndrome

Zu, Shulu; Winberg, Johanna; Arnberg, Fabian; Palmer, Gabriella; Svensson, Pär-Johan; Wester, Tomas; Nordenskjöld, Agneta

doi:10.1016/j.jpedsurg.2011.02.039

Cited by 14 publications

(10 citation statements)

References 28 publications

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“…Pathogenic variants were more commonly identified in females (6/14) than in males (1/11). Of these, only one variant, c.634C>T (p.Gln212*), was previously reported in a Swedish patient [ 10 ]. The other variants were identified for the first time in this study.…”

Section: Resultsmentioning

confidence: 99%

“…Besides these major signs, developmental delays, neural tube defects, sensorineural deafness, and other features such as depressed nasal bridge, joint hyperextensibility, cataracts, ptosis, microcephaly, and facial dysmorphism have been reported in patients with CS [ 2 3 4 ]. Phenotypic variability has also been observed in these patients, with some of the major signs not being observed in incomplete cases [ 5 6 7 8 9 10 11 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…At least 82 MNX1 heterozygous pathogenic variants have been reported to date [ 18 ]; two studies on MNX1 pathogenic variants in Korean patients with CS have been conducted, which included three familial cases and two sporadic cases [ 9 19 ]. However, these pathogenic variants have been identified only in familial cases; moreover, reduced penetrance and variable expressivity of the MNX1 pathogenic variants in CS cases have been reported, even in familial cases [ 6 7 8 9 10 11 12 18 19 ]. In this study, we investigated a large number of patients with CS to determine the spectrum of MNX1 pathogenic variants, and described, for the first time, the MNX1 pathogenic variants in Korean patients with sporadic CS.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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BackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsThis study revealed the spectrum and phenotypic variability of MNX1 pathogenic variants in the Korean population.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…Early analysis using a 38K BAC array with whole genome coverage (Swegene DNA Microarray Resource Center, Department of Oncology, Lund University, Sweden) was performed as previously described in individual cases as specified in Table S2 [21].…”

Section: Methodsmentioning

confidence: 99%

Mutation Screening and Array Comparative Genomic Hybridization Using a 180K Oligonucleotide Array in VACTERL Association

et al. 2014

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In order to identify genetic causes of VACTERL association (V vertebral defects, A anorectal malformations, C cardiac defects, T tracheoesofageal fistula, E esophageal atresia, R renal anomalies, L limb deformities), we have collected DNA samples from 20 patients diagnosed with VACTERL or with a VACTERL-like phenotype as well as samples from 19 aborted fetal cases with VACTERL. To investigate the importance of gene dose alterations in the genetic etiology of VACTERL association we have performed a systematic analysis of this cohort using a 180K array comparative genomic hybridization (array-CGH) platform. In addition, to further clarify the significance of PCSK5, HOXD13 and CHD7 genes in the VACTERL phenotype, mutation screening has been performed. We identified pathogenic gene dose imbalances in two fetal cases; a hemizygous deletion of the FANCB gene and a (9;18)(p24;q12) unbalanced translocation. In addition, one pathogenic mutation in CHD7 was detected, while no apparent disease-causing mutations were found in HOXD13 or PCSK5. Our study shows that although large gene dose alterations do not seem to be a common cause in VACTERL association, array-CGH is still important in clinical diagnostics to identify disease cause in individual cases.

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“…With backing in the literature, we now recommend that asymptomatic mutation carriers should be examined with MRI (3,14,25,34), and that presacral tumours (except for small meningoceles) should be removed (3,25,34). Figure 3b and Tom Monclair (born 1942) MD PhD and specialist in paediatric and general surgery.…”

Section: Geneticsmentioning

confidence: 99%

Currarinos syndrom ved Rikshospitalet 1961 – 2012

Monclair¹,

Lundar²,

Smevik³

et al. 2013

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Mutation analysis of the motor neuron and pancreas homeobox 1 (MNX1, former HLXB9) gene in Swedish patients with Currarino syndrome

Cited by 14 publications

References 28 publications

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

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

Mutation Screening and Array Comparative Genomic Hybridization Using a 180K Oligonucleotide Array in VACTERL Association

Currarinos syndrom ved Rikshospitalet 1961 – 2012

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