Abstract
BackgroundTreacher Collins syndrome (TCS, OMIM 154500) is an autosomal disorder of craniofacial development with an incidence rate of 1/50,000 live births. Although TCOF1, POLR1D, and POLR1C, have been identified as the pathogenic genes for about 90% TCS patients, the pathogenic variants of about 8–11% cases remain unknown. The object of this study is to describe the molecular basis of 14 clinically diagnosed TCS patients from four families using Whole-exome sequencing (WES) followed by Sanger sequencing confirmation, and to analyze the effect of bone conduction hearing rehabilitation in TCS patients with bilateral conductive hearing loss.ResultsFour previously unreported heterozygous pathogenic variants (c.3047-2A > G, c.2478 + 5G > A, c.489delC, c.648delC) were identified in the TCOF1 gene, one in each of the four families. Sanger sequencing in family members confirmed co-segregation of the identified TCOF1 variants with the phenotype. The mean pure-tone threshold improvements measured 3 months after hearing intervention were 28.8 dB for soft-band BAHA, 36.6 ± 2.0 dB for Ponto implantation, and 27.5 dB SPL for Bonebridge implantation. The mean speech discrimination improvements measured 3 months after hearing intervention in a sound field with a presentation level of 65 dB SPL were 44%, 51.25 ± 5.06, and 58%, respectively. All six patients undergoing hearing rehabilitation in this study got a satisfied hearing improvement.ConclusionsWES combined with Sanger sequencing enables the molecular diagnosis of TCS and may detect other unknown causative genes. Bone conduction hearing rehabilitation may be an optimal option for TCS patients with bilateral conductive hearing loss.
Highlights
Treacher Collins syndrome (TCS, OMIM 154500) is an autosomal disorder of craniofacial development with an incidence rate of 1/50,000 live births
More than 200 distinct mutations have been reported in TCOF1, accounting for about 70–93% of TCS individuals, which are inherited via an autosomal dominant pattern, while POLR1D and POLR1C mutations have been found in about 11–23% of the remaining patients, which are inherited via autosomal dominant and autosomal recessive patterns, respectively [3, 5,6,7]
Downward slanting palpebral fissures and mandibular hypoplasia were observed in all patients
Summary
Treacher Collins syndrome (TCS, OMIM 154500) is an autosomal disorder of craniofacial development with an incidence rate of 1/50,000 live births. TCOF1, POLR1D, and POLR1C, have been identified as the pathogenic genes for about 90% TCS patients, the pathogenic variants of about 8–11% cases remain unknown. TCS is characterized by typical bilateral craniofacial malformations, such as hypoplasia of the mandible and zygomatic complex, downward-slanting palpebral fissures, coloboma. A diagnosis of TCS has been based on the clinical identification of a minimal clinical phenotype: downward slanting palpebral fissures and hypoplasia of. Fan et al Orphanet Journal of Rare Diseases (2019) 14:178 the zygomatic arch This can overlook some mildly affected patients. More than 200 distinct mutations have been reported in TCOF1, accounting for about 70–93% of TCS individuals, which are inherited via an autosomal dominant pattern, while POLR1D and POLR1C mutations have been found in about 11–23% of the remaining patients, which are inherited via autosomal dominant and autosomal recessive patterns, respectively [3, 5,6,7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
