The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach

Reis, Larissa Brussa; Turchetto‐Zolet, Andreia Carina; Fonini, Maievi; Ashton‐Prolla, Patrícia; Rosset, Clévia

doi:10.3390/genes10110839

Cited by 3 publications

(2 citation statements)

References 46 publications

(53 reference statements)

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“…Several studies have indicated the correlation between RNF135 mutations and neuronal diseases. The RNF135 gene is located in a chromosomal region that is often frequently absent in patients with neurofibromatosis ( 27 , 28 ). Furthermore, Tastet et al ( 29 ) showed a significant increase in the frequency of genotypes carrying a missense variant of the rare allele rs111902263 (p.R115K) in a cohort of French patients with autism, while three unrelated patients showed a homozygous genotype for K115.…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identifies novel inherited genetic variants in tetralogy of Fallot

Pan¹,

Liu²,

Zhang³

et al. 2022

J Thorac Dis

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Background: Tetralogy of Fallot (TOF) is the most common neonatal cyanotic heart defect, and genetic variation is an important risk factor for the etiology of TOF. Identifying TOF-associated genetic variants is critical to understanding susceptibility and outcome in patients with TOF and may help delineate pathological mechanisms.Methods: Whole exome sequencing (WES) was performed 19 patients with sporadic TOF and 3 healthy controls. The dbSNP, GnomAD, Denovo-db, and ClinVar databases were used to annotate the mutations.PolyPhen, SIFT, MutationTaster, and FATHMM softwares were used for mutation pathogenicity analysis.Sanger sequencing was used to validate candidate variants. Results:We identified 21 genetic variants involving 16 genes were found in 12 patients with sporadic TOF.The types of mutations were missense and splicing variants. None of these genes were detected in samples from the 3 healthy controls. These variants include 9 pathogenic variants, 6 suspected pathogenic variants, and 6 variants of unknown significance (VUS). Further analysis showed that the patients with apolipoprotein B (APOB) and ring finger protein 135 (RNF135) variants had more serious clinical symptoms. Sanger sequencing confirmed that the two variants were heterozygous in TOF patients. Conclusions:We identified several genetic variants associated with TOF and confirmed that RNF135 and ABOB variants were associated with TOF severity. These findings provide new evidence for exploring the genetic mechanism of TOF.

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Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identifies novel inherited genetic variants in tetralogy of Fallot

Pan¹,

Liu²,

Zhang³

et al. 2022

J Thorac Dis

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“…Young children with microdeletions grow taller and heavier than those without these deletions ( 69 ). In addition, both loss-of-function mutations of ring finger protein 135 (RNF135) and microdeletion of NF1-REPa to REPb including RNF135 contribute to an overgrowth syndrome including tall stature, macrocephaly, dysmorphic features, and variable additional features in NF1 patients ( 38 ).…”

Section: Mutations Of Nf1 or Modifier Genes Related To Different Nf1 Phenotypesmentioning

confidence: 99%

Impacts of NF1 Gene Mutations and Genetic Modifiers in Neurofibromatosis Type 1

et al. 2021

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Neurofibromatosis type 1 (NF1) is a tumor predisposition genetic disorder that directly affects more than 1 in 3,000 individuals worldwide. It results from mutations of the NF1 gene and shows almost complete penetrance. NF1 patients show high phenotypic variabilities, including cafe-au-lait macules, freckling, or other neoplastic or non-neoplastic features. Understanding the underlying mechanisms of the diversities of clinical symptoms might contribute to the development of personalized healthcare for NF1 patients. Currently, studies have shown that the different types of mutations in the NF1 gene might correlate with this phenomenon. In addition, genetic modifiers are responsible for the different clinical features. In this review, we summarize different genetic mutations of the NF1 gene and related genetic modifiers. More importantly, we focus on the genotype–phenotype correlation. This review suggests a novel aspect to explain the underlying mechanisms of phenotypic heterogeneity of NF1 and provides suggestions for possible novel therapeutic targets to prevent or delay the onset and development of different manifestations of NF1.

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Neurofibromatosis-1 microdeletiós szindróma.

Büki

Till

Zsigmond

et al. 2022

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Az 1-es típusú neurofibromatosis autoszomális domináns öröklésmenetet mutató, klinikailag rendkívül heterogén neurocutan kórkép, amelynek kialakulásában elsődlegesen az NF1-gén intragenikus funkcióvesztéses mutációi játszanak szerepet. Ugyanakkor a molekuláris diagnosztika fejlődésének köszönhetően egyre több esetben sikerül kimutatni az NF1-gént és az azzal szomszédos régiókat érintő kópiaszámbeli variánsokat. Genotípus-fenotípus elemzések alapján a pontmutációs eltérések okozta 1-es típusú neurofibromatosis, illetve a microdeletiós eltérések okozta, ún. 17q11.2 microdeletiós szindróma elkülöníthetők egymástól. Microdeletiók az esetek 5–10%-ában figyelhetők meg, melyek méretük, töréspontjaik genomi lokalizációja és érintett géntartalmuk alapján négy különböző típusba (1-es, 2-es, 3-as és atípusos) sorolhatók. A microdeletiós betegek gyakran súlyosabb kórlefolyást mutatnak, melyből kiemelendő a malignitások emelkedett kockázata. Az összefoglaló közleménnyel, mely a neurofibromatosis-1 microdeletiós szindróma főbb jellemzőit, molekuláris genetikai hátterét és vizsgálati módszereit tárgyalja, a microdeletiós szindrómás betegek korai diagnózishoz jutásának fontosságát szeretnénk hangsúlyozni és felhívni a figyelmet a szoros nyomon követés jelentőségére. Orv Hetil. 2022; 163(51): 2041–2051.

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The Role of Co-Deleted Genes in Neurofibromatosis Type 1 Microdeletions: An Evolutive Approach

Cited by 3 publications

References 46 publications

Whole exome sequencing identifies novel inherited genetic variants in tetralogy of Fallot

Whole exome sequencing identifies novel inherited genetic variants in tetralogy of Fallot

Impacts of NF1 Gene Mutations and Genetic Modifiers in Neurofibromatosis Type 1

Neurofibromatosis-1 microdeletiós szindróma.

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