Treacher Collins syndrome with a novel deletion in the TCOF1 gene

Çavdartepe, Büşra Eser

doi:10.14744/etd.2019.62144

“…We report the first systematic approach in the geno-phenotypic characterization of a cohort of individuals clinically diagnosed with TCS in Egypt and Arab countries and which includes the report of novel pathogenic variants (Schlump et al, 2012;Ulusal et al, 2013;Eser Çavdartepe et al, 2019) (Mudau et al, 2021). TCS diagnosis is mainly based on the distinct clinical phenotype; however, as the disease is associated with reduced penetrance and different modes of inheritance, molecular diagnosis is essential to provide patients with proper genetic counseling.…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular study of Egyptian patients with Treacher Collins syndrome

Elbagoury,

Nabil,

Abdel-Aleem

et al. 2023

Clinical Dysmorphology

0

View full text Add to dashboard Cite

Treacher Collins syndrome (TCS) is a rare disorder of craniofacial development following different patterns of inheritance. To date, mutations in four genes (TCOF1, POLR1D, POLR1C, and POLR1B) have been found to cause the condition. The molecular defect remains unidentified in a significant proportion of patients. In the current study, whole exome sequencing including analysis of copy number variants was applied for genetic testing of eight Egyptian patients with typical TCS phenotype, representing the first molecular analysis of TCS patients in Egypt as well as in Arab countries. Five heterozygous frameshift mutations were reported, including four variants in the TCOF1 gene (c.3676_3694delinsCTCTGG, c.3984_3985delGA, c.4366_4369delGAAA, and c.3388delC) and one variant in the POLR1D gene (c.60dupA). Four variants were novel extending the disease mutation spectrum. In three affected individuals, no variants of interest were identified in genes associated with TCS or clinically overlapping conditions. Additionally, no relevant variant was detected in genes encoding other subunits of RNA polymerase (pol) I. Molecular analysis is important to provide accurate genetic counseling. It would also contribute to reduced disease incidence. Further studies should be designed to investigate other possible etiologies when no pathogenic variants were revealed in either of the known genes.

show abstract

The role of genetic factors in microtia: A systematic review

Putri

¹

,

Stephanie²,

Pramanasari³

et al. 2022

View full text Add to dashboard Cite

Background: Microtia is a congenital malformation of the outer ears caused by improper embryonic development. The origin of microtia and causes of its variations remain unknown. Because of the lack of clarity regarding the role of genetic variables in microtia, we conducted a systematic review to qualitatively identify the genes most important in the development of microtia to provide an up-to-date review. Methods: Using six search engines, we searched all published studies related to the genetic factors of isolated microtia and syndromic microtia. The identified publications were screened and selected based on inclusion and exclusion criteria by the authors and assessed for methodological quality using the Joanna Briggs Institute (JBI) critical appraisal tools. We found 40 studies, including 22 studies on syndromic microtia and 18 studies on isolated microtia. Data extraction of each study was arranged in tabulation for syndromic and isolated microtia. The extracted data were: first author’s surname, year of publication, country of origin, study design, sample characteristic and gene assessed. Results: After the data were extracted, analyzed, and reviewed, the most common gene suspected to be involved in isolated microtia was Homeobox A2 (HOXA2, 12.1%). Conversely, in syndromic microtia, the two most common genes supposed to play a role were Fibroblast Growth Factor 3 (FGF3, 47.2%) and Treacher–Collins–Franceschetti syndrome 1 (TCOF1, 30.2%). From the studies, the three most prevalent genes associated with microtia were HOXA2 (10%), FGF3 (8.4%), and TCOF1 (5.4%). In syndromic microtia, the most common mutation types were deletion in TCOF1 (46.9%) and missense and deletion in FGF3 (both 38%), and in isolated microtia, the most common mutation type was silent in HOXA2 (54.2%). Conclusions: In summary, genetic factors are involved in microtia; thus, molecular analysis is strongly advised. PROSPERO registration: CRD42021287294 (25/10/21).

show abstract

The role of genetic factors in microtia: A systematic review

Putri

¹

,

Stephanie

²

,

Pramanasari

³

et al. 2023

View full text Add to dashboard Cite

Background: Microtia is a congenital malformation of the outer ears caused by improper embryonic development. The origin of microtia and causes of its variations remain unknown. Because of the lack of clarity regarding the role of genetic variables in microtia, we conducted a systematic review to qualitatively identify the genes most important in the development of microtia to provide an up-to-date review. Methods: Using six search engines, we searched all published studies related to the genetic factors of isolated microtia and syndromic microtia. The identified publications were screened and selected based on inclusion and exclusion criteria by the authors and assessed for methodological quality using the Joanna Briggs Institute (JBI) critical appraisal tools. We found 40 studies, including 22 studies on syndromic microtia and 18 studies on isolated microtia. Data extraction of each study was arranged in tabulation for syndromic and isolated microtia. The extracted data were: first author’s surname, year of publication, country of origin, study design, sample characteristic and gene assessed. Results: After the data were extracted, analyzed, and reviewed, the most common gene suspected to be involved in isolated microtia was Homeobox A2 (HOXA2, 12.1%). Conversely, in syndromic microtia, the two most common genes supposed to play a role were Fibroblast Growth Factor 3 (FGF3, 47.2%) and Treacher–Collins–Franceschetti syndrome 1 (TCOF1, 30.2%). From the studies, the three most prevalent genes associated with microtia were HOXA2 (10%), FGF3 (8.4%), and TCOF1 (5.4%). In syndromic microtia, the most common mutation types were deletion in TCOF1 (46.9%) and missense and deletion in FGF3 (both 38%), and in isolated microtia, the most common mutation type was silent in HOXA2 (54.2%). Conclusions: In summary, genetic factors are involved in microtia; thus, molecular analysis is strongly advised. PROSPERO registration: CRD42021287294 (25/10/21).

show abstract

Treacher Collins syndrome with a novel deletion in the TCOF1 gene

Cited by 3 publications

References 10 publications

Clinical and molecular study of Egyptian patients with Treacher Collins syndrome

Clinical and molecular study of Egyptian patients with Treacher Collins syndrome

The role of genetic factors in microtia: A systematic review

The role of genetic factors in microtia: A systematic review

Contact Info

Product

Resources

About