Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Precision Medicine Center, Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
Mol Genet Genomic Med. 2021 Feb;9(2):e1573. doi: 10.1002/mgg3.1573. Epub 2020 Dec 17.
Treacher Collins syndrome-1 (TCS1; OMIM# 154500) is a rare autosomal dominant disease that is defined by congenital craniofacial dysplasia. Here, we report four sporadic and one familial case of TCS1 in Chinese patients with clinical features presenting as hypoplasia of the zygomatic complex and mandible, downslanting palpebral fissures, coloboma of the lower eyelids, and conductive hearing loss.
Audiological, radiological, and physical examinations were performed. Targeted next-generation sequencing (NGS) was performed to examine the genetics of this disease in five probands, and Sanger sequencing was used to confirm the identified variants. A literature review discusses the pathogenesis, treatment, and prevention of TCS1.
We identified a novel insertion of c.939_940insA (p.Gly314Argfs35; NM_001135243.1), a novel deletion of c.1766delC (p.Pro589Leufs7), two previously reported insertions of c.1999_2000insC (p.Arg667Profs31) and c.4218_4219insG (p.Ser1407Valfs23), and one previously reported deletion of c.4369_4373delAAGAA (p.Lys1457Glufs*12) in the TCOF1 gene. All five cases exhibited a degree of interfamilial and intrafamilial phenotypic variability. A review of the literature revealed no clear evidence of a genotype-phenotype correlation in TCS1.
Our results expand the variant spectrum of TCOF1 and highlight that NGS is essential for the diagnosis of TCS and that genetic counseling is beneficial for guiding prevention.
Treacher Collins 综合征-1（TCS1；OMIM#154500）是一种罕见的常染色体显性疾病，其特征为先天性颅面发育不良。本研究报道了 4 例散发和 1 例家族性 TCS1 病例，临床表现为颧骨复合体和下颌骨发育不全、下斜型睑裂、下眼睑裂、传导性听力损失。
进行了听力学、影像学和体格检查。对 5 个先证者进行了靶向下一代测序（NGS）检查，以检查该疾病的遗传学，并使用 Sanger 测序对鉴定的变体进行了验证。文献综述讨论了 TCS1 的发病机制、治疗和预防。
我们发现了一个新的 c.939_940insA（p.Gly314Argfs35；NM_001135243.1）插入，一个新的 c.1766delC（p.Pro589Leufs7）缺失，两个先前报道的 c.1999_2000insC（p.Arg667Profs31）和 c.4218_4219insG（p.Ser1407Valfs23）插入，以及一个先前报道的 c.4369_4373delAAGAA（p.Lys1457Glufs*12）缺失，均位于 TCOF1 基因中。所有五个病例均表现出一定程度的家族内和家族间表型变异性。文献回顾未发现 TCS1 中基因型-表型相关性的明确证据。
我们的结果扩展了 TCOF1 的变异谱，并强调了 NGS 对 TCS 的诊断至关重要，遗传咨询有助于指导预防。
