Severe craniofrontonasal syndrome in a male patient mosaic for a novel nonsense mutation in EFNB1

Shotelersuk, Varote; Kamolvisit, Wuttichart; Rojvachiranonda, Nond; Suphapeetiporn, Kanya; Porntaveetus, Thantrira; Shotelersuk, Vorasuk

doi:10.1016/j.ejmg.2020.103924

Cited by 4 publications

(7 citation statements)

References 16 publications

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“…These two ephrin-B1 forms’ coexistence affects the adhesion and sorting of cells, disrupting normal embryological development [ 6 , 7 ]. Further reports describing more severely affected males, who all were mosaic for deleterious variants in the EFNB1 , strengthen the hypothesis about the described pathomechanism’s biological relevance [ 8 ]. However, the precise molecular explanation for this phenomenon remains not yet fully understood [ 7 ].…”

Section: Introductionmentioning

confidence: 58%

Clinical and molecular characterization of craniofrontonasal syndrome: new symptoms and novel pathogenic variants in the EFNB1 gene

Bukowska‐Olech

Gawliński²,

Jakubiuk‐Tomaszuk

et al. 2021

Orphanet J Rare Dis

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Background Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder that results from pathogenic variants in the EFNB1 gene. The syndrome paradoxically presents with greater severity of the symptoms in heterozygous females than hemizygous males. Results We have recruited and screened a female cohort affected with CFNS. Our primary finding was the description of monozygotic twins, i.e., patients 5 and 6, discordant for the CFNS phenotype. Intriguingly, patient 5 presented classical CFNS gestalt, whereas patient 6 manifested only very subtle craniofacial features, not resembling CFNS. Besides, we have expanded the mutational spectrum of the EFNB1 gene through reporting four novel pathogenic variants—p.(Trp12*), p.(Cys64Phe), p.(Tyr73Metfs*86), p.(Glu210*). All those alterations were found applying either targeted NGS of a custom gene panel or PCR followed by Sanger sequencing and evaluated using in silico predictors. Lastly, we have also expanded the CFNS phenotypic spectrum by describing in patient 3 several novel features of the syndrome, such as bifid hallux, bicornuate uterus, and abnormal right ovary segmented into six parts. Conclusions We have described the unreported so far differences of the clinical phenotype in the monozygotic twin patients 5 and 6 harboring an identical p.(Glu210*) variant located in the EFNB1 gene. With our finding, we have pointed to an unusual phenomenon of mildly affected females with CFNS, who may not manifest features suggestive of the syndrome. Consequently, this study may be valuable for geneticists consulting patients with craniofacial disorders.

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Section: Introductionmentioning

confidence: 58%

Clinical and molecular characterization of craniofrontonasal syndrome: new symptoms and novel pathogenic variants in the EFNB1 gene

Bukowska‐Olech

Gawliński²,

Jakubiuk‐Tomaszuk

et al. 2021

Orphanet J Rare Dis

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“…Our finding shows that there may be a correlation between the severity of phenotype with the location of exon mutation. Legendre et al (2017) and (Shotelersuk et al, 2020) found no significant correlation between phenotype and genotype.…”

Section: Used the Acronym "Charge" (Ocular Coloboma [C] Heart Malform...mentioning

confidence: 83%

“…C. 253C > T (p.Q85*), C. 780del (p.S261Lfs*44), C. 7252C > T (p.R2418*), and C. 5428C > T (P.ARg1810ter) were mainly reported in molecular studies of gene mutations, without specific descriptions of clinical phenotypes (Koenighofer et al, 2015;Zaki et al, 2018;Shotelersuk et al, 2020; Lee et al, 2021). C. 6018DUP (p.S2007Ifs*2) was reported in a study related to endocrine and olfactory, but there was no more phenotypic description (Lin et al, 2020).…”

Section: Used the Acronym "Charge" (Ocular Coloboma [C] Heart Malform...mentioning

confidence: 99%

Discovery of Novel Variants on the CHD7 Gene: A Case Series of CHARGE Syndrome

Chen

Lü

et al. 2022

Front. Genet.

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Background: CHARGE syndrome (CS) is a single-gene genetic disorder with multiple organ malformations caused by a variant of the chromodomain helicase DNA-binding protein 7 (CHD7) gene on chromosome 8q12.1. In this study, we aimed to investigate new variants that have emerged in these cases compared with typical CS and the relationship between the genes and phenotypes.Methods: Patients with suspected genetic diseases were subjected to Whole Exome Sequencing (WES) at a genetics laboratory in Guangzhou. The average sequencing coverage depth was >200 ×, and 96% was >20 ×. The variant interpretation was manipulated according to the American College of Medical Genetics (ACMG) guidelines. Molecular data on databases for ClinVar and CHD7 were also collected and collated. We reviewed the currently described CHD7 variants and analyzed the genetic variation and phenotypic heterogeneity.Results: Data of 12 patients with CS from four hospitals in China were collected. According to gestational age, most of them (8/12) were near-term babies with a lower birth weight than their peers, averaging 2.62 kg. In this study, the most common phenotypes were respiratory tract malformations (11/12), heart malformations (10/12), and central nervous system malformations (9/12). Two fetuses were confirmed to have brain or heart abnormalities during prenatal testing, while 10/12 were found to have abnormalities during prenatal testing. The maximum Acute Physiology and Chronic Health Evaluation (APACHE II) score at admission was 19, and the average was 11.58. Five variants in the CHD7 gene c.7012C > T (p.Q2338*), c.7868delC (p.P2623Rfs*16), c.5405-3C > G, c.6936 + 2T > C, and c.8077-2A > G) were novel and were located in exons 33, 36, and introns 25, 32, and 37, respectively. There may be a positive correlation between exon location and phenotype.Conclusion: Five novel variants were discovered. These expanded the mutational spectrum of the CHD7 gene and the phenotype of CS. There may be a correlation between the new mutation sites and the phenotype, which has some reference value for the evaluation of mutation sites.

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“…Growing interest and use of new powerful sequencing techniques have enabled more systematic identification of a vast number of causative genes that have significantly improved our understanding of the etiology and pathogenesis of human congenital anomalies and diseases, including those affecting the orofacial region (1)(2)(3). This Research Topic issue aimed to provide a platform for studies that feature the most recent research advances in the field of genetics of dental and craniofacial conditions.…”

Section: Editorial On the Research Topic Contemporary Views On The Ge...mentioning

confidence: 99%

Editorial: Contemporary Views on the Genetics of Dental and Craniofacial Anomalies

Porntaveetus¹,

Abid²,

Seppälä³

2022

Front. Dent. Med

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Severe craniofrontonasal syndrome in a male patient mosaic for a novel nonsense mutation in EFNB1

Cited by 4 publications

References 16 publications

Clinical and molecular characterization of craniofrontonasal syndrome: new symptoms and novel pathogenic variants in the EFNB1 gene

Clinical and molecular characterization of craniofrontonasal syndrome: new symptoms and novel pathogenic variants in the EFNB1 gene

Discovery of Novel Variants on the CHD7 Gene: A Case Series of CHARGE Syndrome

Editorial: Contemporary Views on the Genetics of Dental and Craniofacial Anomalies

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