2.TCOF1 Gene variation in Treacher Collins syndrome and evaluation of speech rehabilitation after bone bridge surgery.
Yonghua LI ; Wenyue CHI ; Ken LIN ; Jinyan ZU ; Hua SHAO ; Zhiyong MAO ; Quandong CHEN ; Jing MA
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(9):748-754
Objective:By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome(TCS), the biological causes of the disease were determined. Then discuss the therapeutic effect of hearing intervention after bone bridge implantation. Methods:All clinical data of the two family members were collected, and the patients signed the informed consent. The peripheral blood of the proband and family members was extracted, DNA was extracted for whole exome sequencing, and Sanger sequencing was performed on the family members for the mutation site.TCOF1genetic mutations analysis was performed on the paitents. Then, the hearing threshold and speech recognition rate of family 2 proband were evaluated and compared under the sound field between bare ear and wearing bone bridge. Results:In the two pedigrees, the probands of both families presented with auricle deformity, zygomatic and mandibular hypoplasia, micrognathia, hypotropia of the eye fissure, and hypoplasia of the medial eyelashes. The proband of Family 1 also presents with specific features including right-sided narrow anterior nasal aperture and dental hypoplasia, which were consistent with the clinical diagnosis of Treacher Collins syndrome. Genetic testing was conducted on both families, and two heterozygous mutations were identified in the TCOF1 gene: c. 1350_1351dupGG(p. A451Gfs*43) and c. 4362_4366del(p. K1457Efs*12), resulting in frameshift mutations in the amino acid sequence. Sanger sequencing validation of the TCOF1 gene in the parents of the proband in Family 1 did not detect any mutations. Proband 1 TCOF1 c. 1350_1351dupGG heterozygous variants have not been reported previously. The postoperative monosyllabic speech recognition rate of family 2 proband was 76%, the Categories of Auditory Performance(CAP) score was 6, and the Speech Intelligibility Rating(SIR) score was 4. Assessment using the Meaningful Auditory Integration Scale(MAIS) showed notable improvement in the patient's auditory perception, comprehension, and usage of hearing aids. Evaluation using the Glasgow Children's Benefit Inventory and quality of life assessment revealed significant improvements in the child's self care abilities, daily living and learning, social interactions, and psychological well being, as perceived by the parents. Conclusion:This study has elucidated the biological cause of Treacher Collins syndrome, enriched the spectrum of TCOF1 gene mutations in the Chinese population, and demonstrated that bone bridge implantation can improve the auditory and speech recognition rates in TCS patients.
Child
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Humans
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Mandibulofacial Dysostosis/genetics*
;
Quality of Life
;
Speech
;
Parents
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Mutation
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Nuclear Proteins/genetics*
;
Phosphoproteins/genetics*
3.Pathogenic genes and clinical therapeutic strategies for Treacher Collins syndrome.
Bin YIN ; Bing SHI ; Zhong-Lin JIA
West China Journal of Stomatology 2019;37(3):330-335
Treacher Collins syndrome is a congenital craniofacial malformation with autosomal dominant inheritance as the main genetic pattern. In this condition, the biosynthesis of ribosomes in neural crest cells and neuroepithelial cells is blocked and the number of neural crest cells that migrate to the craniofacial region decreases, causing first and second branchial arch dysplasia. Definite causative genes include treacle ribosome biogenesis factor 1 (tcof1), RNA polymerase Ⅰ and Ⅲ subunit C (polr1c), and RNA polymerase Ⅰ and Ⅲ subunit D (polr1d). This paper provides a review of research of three major patho-genic genes, pathogenesis, phenotypic research, prevention, and treatment of the syndrome.
DNA-Directed RNA Polymerases
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genetics
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Humans
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Mandibulofacial Dysostosis
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genetics
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Neural Crest
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Nuclear Proteins
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Phosphoproteins
4.The research progress of Treacher Collins syndrome.
Pu WANG ; Xinmiao FAN ; Yue FAN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2016;30(4):333-338
Treacher Collins syndrome (TCS, OMIM 154500), also known as Franceschetti-Klein syndrome, is a rare disorder that affects the first and second branchial arches. The estimated incidence is 1/50 000 live births. Mutations in TCOF1 (78%-93%) and POLR1C or POLR1D (8%) cause the disease. Most of TCS cases are inherited in a dominant pattern, while a small proportion are inherited in a recessive pattern. TCS has a variable phenotype with typical clinical characteristics including downward-slant of palpebral fissure, malar hypoplasia, mandibular hypoplasia and microtia. TCS management is a multidisciplinary affair, as interventions range from reconstructive to psychosocial. For hearing rehabilitation, TCS patients may have the choices of BAHA, ponto, vibrant soundbridge or bonebridge implantation. In this review, we summarize the TCS clinical malformations, diagnosis, genetics, management and auditory rehabilitation.
DNA-Directed RNA Polymerases
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genetics
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Facial Bones
;
abnormalities
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Humans
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Mandibulofacial Dysostosis
;
diagnosis
;
genetics
;
rehabilitation
;
Mutation
;
Nuclear Proteins
;
genetics
;
Phosphoproteins
;
genetics
5.Clinical and genetic analysis of a patient with Treacher Collins syndrome in TCOF1 gene.
Hongbo LI ; Xu ZHANG ; Zhenyue LI ; Jing CHEN ; Yu LU ; Jingjie JIA ; Huijun YUAN ; Dongyi HAN
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2012;26(10):459-462
OBJECTIVE:
To analyze the clinical and genetic features of a patient with Treacher Collins syndrome (TCS), and identify the mutation in TCOF1 gene.
METHOD:
The medical history was taken, and general physical examinations and otological examinations were conducted in this patient. Genomic DNA was extracted from this patient and his parents and complete TCOF1 gene coding exons were amplified by specific PCR primers. Direct sequencing was carried out to identify the mutations. The raw data was analyzed with GeneTool software and molecular biological website.
RESULT:
We detected a heterozygous c. 1639 delAG mutation in exon 11 of TCOF1, which resulted in a truncated protein lacking normal function. This mutation is a novel mutation and the second case identified in exon 11 of in TCS.
CONCLUSION
TCS patient reported in this study has unique clinical phenotype. TCOF1 gene mutation is the specific risk factor.
DNA Primers
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Exons
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Genes, Regulator
;
Genetic Testing
;
Humans
;
Mandibulofacial Dysostosis
;
diagnosis
;
genetics
;
Mutation
;
Nuclear Proteins
;
genetics
;
Phenotype
;
Phosphoproteins
;
genetics
;
Syndrome
6.Genetic analysis of a rare fetus with mandibulofacial dysostosis Guion-Almeida type.
Lulu YAN ; Liyun TIAN ; Juan CAO ; Bihua ZHOU ; Yuxin ZHANG ; Yingwen LIU ; Chunxiao HAN ; Haibo LI
Chinese Journal of Medical Genetics 2021;38(8):791-794
OBJECTIVE:
To delineate the clinical and genetic features of a fetus with micrognathia, low-set ears, microtia, polyhydramnios and anechoic stomach by ultrasonography.
METHODS:
Whole exome sequencing (WES) was carried out to detect genetic variant in the fetus, for which routine chromosomal karyotyping and chromosomal microarray analysis (CMA) yielded no positive finding. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.
RESULTS:
WES revealed that the fetus has carried a de novo nonsense c.2302C>T (p.Q768X) variant in exon 23 of the EFTUD2 gene, which was detected in neither parent. The variant was unreported previously and may lead to premature termination of the translation of EFTUD2 protein at the 768th amino acid. Bioinformatic analysis predicted the amino acid to be highly conserved and may alter the structure and function of the EFTUD2 protein.
CONCLUSION
The c.2302C>T variant of the EFTUD2 gene probably underlay the mandibulofacial dysostosis Guion-Almeida type in the fetus. Discovery of the novel variant has enriched variant spectrum of the EFTUD2 gene and provided a basis for genetic counseling and prenatal diagnosis for the family.
Female
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Fetus
;
Humans
;
Mandibulofacial Dysostosis/genetics*
;
Mutation
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Peptide Elongation Factors/genetics*
;
Phenotype
;
Pregnancy
;
Ribonucleoprotein, U5 Small Nuclear/genetics*
7.Prenatal diagnosis of a fetus in a family with mandibulofacial dysostosis.
Yan-hui LIU ; Shao-quan SHI ; Yan-liang ZHANG ; Yong DAI ; Xuan SHANG ; Ya-min WU ; Chao-qiang LI ; Li-fen LI
Chinese Journal of Medical Genetics 2010;27(4):437-440
OBJECTIVETo measure the feasibility of application of comparative genomic hybridization technique in the prenatal diagnosis of fetus with mandibulofacial dysostosis.
METHODSA pregnant woman having a fetus with mandibulofacial dysostosis diagnosed by prenatal ultrasound test was selected. The amniotic fluid and blood of the pregnant and blood of her husband were collected and conventional cytogenetic analysis was performed. The whole genome was scanned by array comparative genomic hybridization assay (array-CGH). Reverse transcription fluorescence quantitative PCR (RT-qPCR) analysis was used to verify the result of array-CGH.
RESULTSNo abnormality was found in conventional cytogenetic analysis while a duplicated region in 1p36.33 was detected by array-CGH assay. The region spans 722 kb and contains two genes, VWA1 and PYGO2, which play roles in the development of cartilage. The result of array-CGH was confirmed by the RT-qPCR assay. The diagnosis of mandibulofacial dysostosis was confirmed after birth.
CONCLUSIONAuthor diagnosed a fetus with mandibulofacial dysostosis by array-CGH assay and found two candidate genes related to the development of craniofacial bone: VWA1 and PYGO2.
Adult ; Chromosome Aberrations ; Comparative Genomic Hybridization ; methods ; Female ; Fetus ; pathology ; Humans ; Karyotyping ; methods ; Mandibulofacial Dysostosis ; genetics ; Pregnancy ; Prenatal Diagnosis ; methods