Treacher Collins syndrome: Clinical report and retrospective analysis of Chinese patients

Pan, Zhaoyu; Xu, Hongen; Chen, Bei; Tian, Yongan; Zhang, Linlin; Zhang, Sen; Liu, Danhua; Liu, Huanfei; Li, Ruijun; Hu, Xinxin; Guan, Jingyuan; Tang, Wenxue; Lü, Wei

doi:10.1002/mgg3.1573

Cited by 7 publications

(10 citation statements)

References 36 publications

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“…Researchers analyzed TCS1 patients with TCOF1 variation in different populations, the results showed that exon 10, exon 15, exon 16, exon 23 and exon 24 were the hotspots of gene variation (Splendore et al, 2002). Pan et al (2021) showed that the hot spots of variants related to TCS1 in the Chinese population were located in exon 5, exon 23 and exon 24, which were different from the hot spot variants of TCOF1 gene in the two children in this study. According to the human genome mutation database (HGMD), more than 367 sites of variants have been reported in the TCOF1 gene.…”

Section: Discussionmentioning

confidence: 60%

“…TCS1 is a rare autosomal dominant disorder defined as congenital craniofacial dysplasia, characterized by unique “bird‐shaped” facial manifestations (malar and mandibular dysplasia, etc.) and conductive hearing loss (auricle, external auditory canal and middle ear malformations) (Pan et al., 2021 ). The main cause of TCS1 is the variants in TCOF1 locus, which is located on chromosome 5q32‐q33.1, containing 28 exons and encoding 4465 base pairs (Zhang et al., 2013 ); It also encodes a low‐complexity, and serine/alanine‐rich protein called the Treacle protein, which is composed of 1488 amino acids with a molecular weight of about 152 KD, and has three domains, namely the N‐terminal and C‐terminal, and a central repetitive domain (Pan et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…(Walker‐Kopp et al., 2017 ). To date, only four pathogenic genes ( TCOF1 gene, POLR1B gene, POLR1D gene and POLR1C gene) have been identified as the cause of 90% of TCS patients (Fan et al., 2019 ; Pan et al., 2021 ), most of these patients are caused by TCOF1 gene variation. TCOF1 variants were associated with the clinical phenotype of TCS patients.…”

Section: Introductionmentioning

confidence: 99%

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Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome

Zhuang,

Sun,

et al. 2024

Molec Gen & Gen Med

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BackgroundTreacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology.MethodsThe clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing.ResultsProband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before.ConclusionOur study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome

Zhuang,

Sun,

et al. 2024

Molec Gen & Gen Med

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“…Variant (NM_000356.3: c.4131_4135del, p.Lys1380Glufs*12) detected in sporadic patient T2220150810 was already known in previous reports. The variant (NM_000356.3: c.1535del, p.Pro512Leufs*7) was also a known one because patient T3720160105 was the same 1 as case 5 in the study of Pan et al (Pan et al, 2021). An SNP within POLR1D (NM_015972.3: c.139G>A, p.Glu47Lys) was detected in sporadic patient T1020160503 (Table 2).…”

Section: Resultsmentioning

confidence: 96%

Phenotype Analysis and Genetic Study of Chinese Patients With Treacher Collins Syndrome

Lü

Yang

Chen

et al. 2021

The Cleft Palate-Craniofacial Journal

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Objective The aim of this study was to confirm the pathogenic variants, explore the genotype–phenotype correlation and characteristics of Chinese patients with Treacher Collins syndrome (TCS). Design Clinical details of 3 TCS family cases and 2 sporadic cases were collected and analyzed. Whole-exome sequencing and Sanger sequencing were conducted to detect causative variants. Setting Tertiary clinical care. Patients This study included 8 patients clinically diagnosed with TCS who were from 3 familial cases and 2 sporadic cases. Main Outcome Measures When filtering the database, variants were saved as rare variants if their frequency were less than 0.005 in the 1000 Genomes Project Database, the Exome Aggregation Consortium (ExAC) browser, and the Novogene database, or they would be removed as common ones. The pathogenic variants identified were verified by polymerase chain reaction. The sequencing results were analyzed by Chromas 2.1 software. Results Two novel pathogenic variants (NM_000356.3: c.537del and NM_000356.3: c.1965_1966dupGG) and 2 known pathogenic variants (NM_000356.3: c.1535del, NM_000356.3: c.4131_4135del) were identified within TCOF1 which are predicted to lead to premature termination codons resulting in a truncated protein. There was a known missense SNP (NM_015972.3: c.139G>A) within POLR1D. No phenotype–genotype correlation was observed. Instead, these 8 patients demonstrated the high genotypic and phenotypic heterogeneity of TCS. Conclusions This study expands on the pathogenic gene pool of Chinese patients with TCS. Besides the great variation among patients which is similar to international reports, Chinese patients have their own characteristics in clinical phenotype and pathogenesis mutations.

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“…Of the 394 initial screened literature records, 334 records were excluded after reviewing the abstract, while 60 full articles were assessed for eligibility, 10 of them were excluded (due to no clinical features data), resulting in 43 TCOF1 1,2,8,13,17–55 and 10 POLR1 related studies 1,4,5,7,17,55–58 . Among them, there were three studies including both TCOF1 and POLR1D 1,17,55 .…”

Section: Resultsmentioning

confidence: 99%

A systematic review on Treacher Collins syndrome: Correlation between molecular genetic findings and clinical severity

et al. 2022

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Treacher Collins syndrome (TCS, OMIM: 154500) is a rare congenital craniofacial disorder that is caused by variants in the genes TCOF1, POLR1D, POLR1C, and POLR1B. Studies on the association between phenotypic variability and their relative variants are very limited. This systematic review summarized the 53 literatures from PubMed and Scopus to explore the potential TCS genotype-phenotype correlations with statistical analysis. Studies reporting both complete molecular genetics and clinical data were included. We identified that the molecular anomaly within TCOF1 (88.71%) accounted for most TCS cases. The only true hot spot for TCOF1 was detected in exon 24, with recurrent c.4369_4373delAAGAA variant is identified.While the hot spot for POLR1D, POLR1C, and POLR1B were identified in exons 3, 8, and 15, respectively. Our result suggested that the higher severity level was likely to be observed in Asian patients harboring TCOF1 variants rather than POLR1. Moreover, common 5-bp deletions tended to have a higher severity degree in comparison to any variants within exon 24 of TCOF1. In summary, this report suggested the relationship between genetic and clinical data in TCS. Our findings could be used as a reference for clinical diagnosis and further biological studies.

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Treacher Collins syndrome: Clinical report and retrospective analysis of Chinese patients

Cited by 7 publications

References 36 publications

Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome

Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome

Phenotype Analysis and Genetic Study of Chinese Patients With Treacher Collins Syndrome

A systematic review on Treacher Collins syndrome: Correlation between molecular genetic findings and clinical severity

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