Atypical 581-kb 22q11.21 Deletion in a Patient with Oculo-Auriculo-Vertebral Spectrum Phenotype

Colovati, Mileny Esbravatti Stephano; Bragagnolo, Silvia; Guilherme, Roberta Santos; Dantas, Anelisa Gollo; Soares, Maria Raquel; Kim, Chong; Pérez, Ana B.; Melaragno, Maria Isabel

doi:10.1159/000444228

Cited by 13 publications

(11 citation statements)

References 26 publications

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“…Moreover, downregulation of Rarb and Cyp26a1 (but also of Rara) 15 was observed in LgDel-22q11 mice and patients with OAVS features carried 22q11 deletions. 5,16 As shown with RARG, 17 our results suggest that RARB could participate in CYP26A1 regulation. Moreover, Cyp26A1 − / − embryos present malformations of the hindbrain, 18 where Myt1, Cyp26A1 and Rarb are expressed, 18,19 and where RA signaling pathway activity is detected.…”

Section: Discussionsupporting

confidence: 73%

A novel de novo mutation in MYT1, the unique OAVS gene identified so far

et al. 2017

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Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by hemifacial microsomia associated with ear, eyes and vertebrae malformations showing highly variable expressivity. Recently, MYT1, encoding the myelin transcription factor 1, was reported as the first gene involved in OAVS, within the retinoic acid (RA) pathway. Fifty-seven OAVS patients originating from Brazil were screened for MYT1 variants. A novel de novo missense variant affecting function, c.323C>T (p.(Ser108Leu)), was identified in MYT1, in a patient presenting with a severe form of OAVS. Functional studies showed that MYT1 overexpression downregulated all RA receptors genes (RARA, RARB, RARG), involved in RA-mediated transcription, whereas no effect was observed on CYP26A1 expression, the major enzyme involved in RA degradation, Moreover, MYT1 variants impacted significantly the expression of these genes, further supporting their pathogenicity. In conclusion, a third variant affecting function in MYT1 was identified as a cause of OAVS. Furthermore, we confirmed MYT1 connection to RA signaling pathway.

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Section: Discussionsupporting

confidence: 73%

A novel de novo mutation in MYT1, the unique OAVS gene identified so far

et al. 2017

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“…Chromosomal alterations have been reported in several cases and regions located at 22q were the main findings described in OAVS individuals. In our review, we observed that deletions and duplications in regions 22q11.1 (Beleza‐Meireles et al, 2015) and 22q11.2 (Beleza‐Meireles et al, 2015; Bragagnolo et al, 2018; Colovati et al, 2015; dos Santos et al, 2014; Spineli‐Silva et al, 2018; Xu et al, 2008) were the main findings in individuals with the phenotype. However, these regions comprise a lot of genes with unknown function as many pseudogenes.…”

Section: Discussionmentioning

confidence: 76%

“…Despite the unclear etiology of OAVS, some studies have already detected loci candidates through linkage studies (Beleza‐Meireles et al, 2015; Kelberman et al, 2001) and epigenetic inheritance (Fischer et al, 2006). Among chromosomal abnormalities, chromosome region 22q11.2 is the most frequently reported (Beleza‐Meireles et al, 2015; Colovati et al, 2015; Derbent et al, 2003; dos Santos et al, 2014; Lafay‐Cousin et al, 2009; Spineli‐Silva et al, 2018; Tan et al, 2011; Torti, Braddock, Bernreuter, & Batanian, 2013; Xu, Fan, & Siu, 2008). Low copy repeats (LCRs) in 22q11.2 region have been directly implicated in its chromosomal rearrangements.…”

Section: Introductionmentioning

confidence: 99%

“…Low copy repeats (LCRs) in 22q11.2 region have been directly implicated in its chromosomal rearrangements. Those small DNA sequences can lead to a genomic instability, mediate nonallelic homologous recombination (NAHR) or stimulate the occurrence of copy number variation that may result in the deletion or duplication of a genomic segment (Colovati et al, 2015; Stankiewicz & Lupski, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Candidate genes of oculo‐auriculo‐vertebral spectrum in 22q region: A systematic review

Glaeser

Santos

Diniz

et al. 2020

American J of Med Genetics Pt A

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Oculo-auriculo-vertebral spectrum (hemifacial microsomia/OAVS, OMIM #164210) is a heterogenous and congenital condition caused by a morphogenesis defect of the first and second pharyngeal arches. Etiology includes unknown genetic, environmental factors and chromosomal alterations, which 22q11.2 region is the most frequently reported. Several candidate genes for OAVS have been proposed; however, none has been confirmed as causative of the phenotype. This review aims to sum up all clinical and molecular findings in 22q region of individuals diagnosed with OAVS and to investigate genes that may be involved in the development of the spectrum. A search was performed in PubMed using all entry terms to OAVS and Chromosome 22q11. After screening, 11 papers were eligible for review. Deletions and duplications in the q11.2 region were the most frequent (18/22) alterations reported and a total of 68 genes were described. Our systematic review reinforces the hypothesis that 22q11 region is a candidate locus for OAVS as well as CLTCL1, GSC2, HIRA, MAPK1, TBX1, and YPEL1 as potential candidates genes for genotype-phenotype correlation. Complementary studies regarding genes interaction involved in the 22q11 region are still necessary in the search for a genotype-phenotype association, since the diagnosis of OAVS is a constant medical challenge.

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“…These syndromes include: Treacher Collins' syndrome (OMIM 154500), auriculocondylar syndrome (OMIM 602483), 12 Townes-Brocks' syndrome (OMIM 107480), 9,19 cri du chat syndrome (OMIM 123450), 20 oculoauricular syndrome (OMIM 612109), branchio-otorenal syndrome 1 (OMIM 113650), cat eye syndrome (OMIM 115470), and otofaciocervical contiguous gene deletion syndrome (OMIM 166780). 1 Deletions and duplications on chromosome 22 in regions 22q11.2 causing DiGeorge's syndrome (DGS; OMIM 188400), 1,6,8,[21][22][23] 22q11.1, 6 22q13.32-33, 6 and 22q13.3 24 should also be considered.…”

Section: Problems Of Differential Diagnosismentioning

confidence: 99%

Microarray-Based Comparative Genomic Hybridization, Multiplex Ligation-Dependent Probe Amplification, and High-Resolution Karyotype for Differential Diagnosis Oculoauriculovertebral Spectrum: A Systematic Review

et al. 2020

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Oculoauriculovertebral spectrum (OAVS) is a rare class of heterogenous congenital craniofacial malformation conditions of unknown etiology. Although classic OAVS has been described as hemifacial microsomia with facial asymmetry and microtia, there is no consensus regarding clinical criteria for diagnosis or genetic cause. This systematic review aims to assess the applicability of high-resolution (HR) karyotype, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA), and microarray-based comparative genomic hybridization (array-CGH) for differential diagnosis of OAVS. A search was performed in PubMed and Web of Science using all entry terms to the following descriptors: Goldenhar's syndrome, cytogenetic analysis, hybridization in situ, fluorescent, comparative genomic hybridization, multiplex polymerase chain reaction, whole genome sequencing, and karyotype analysis methods. After screening, 25 articles met eligibility. Of the included studies, 59 individuals had a genetic alteration identified. Array-CGH, MLPA, and HR karyotype appear to be viable approaches for molecular diagnosis in OAVS. Heterogeneity is a hallmark of OAVS. Establishing an enhanced framework for diagnosis would inform clinical decision making, and better resource utilization could improve health care facility efficiency and economy.

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Atypical 581-kb 22q11.21 Deletion in a Patient with Oculo-Auriculo-Vertebral Spectrum Phenotype

Cited by 13 publications

References 26 publications

A novel de novo mutation in MYT1, the unique OAVS gene identified so far

A novel de novo mutation in MYT1, the unique OAVS gene identified so far

Candidate genes of oculo‐auriculo‐vertebral spectrum in 22q region: A systematic review

Microarray-Based Comparative Genomic Hybridization, Multiplex Ligation-Dependent Probe Amplification, and High-Resolution Karyotype for Differential Diagnosis Oculoauriculovertebral Spectrum: A Systematic Review

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