Orphanet journal of rare diseases · 2025
Identification of novel TCOF1 mutations in Treacher Collins syndrome and their functional characterization.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Chen Ying, Yang Run, Chen Xin, Zhang Tianyu, Li Chenlong, Ma Jing
Аннотация
BACKGROUND: Treacher Collins syndrome (TCS) is a congenital disorder primarily caused by the mutation in the Treacle Ribosome Biogenesis Factor 1 (TCOF1) gene. However, the significance of many TCOF1 mutations remains uncertain.
RESULTS: We report two novel mutations identified in two TCS families and assess their pathogenicity alongside two previously reported mutations. Both novel mutations, c.2115dupG (p.T706DfsTer52) and c.2142+23_2142+52 del (p.A715VfsTer31), result in truncated proteins lacking nuclear location signals (NLSs), which impedes their entry into the nucleus and reduces mRNA expression level. Notably, the mutation c.2142+23_2142+52 del, leading to the retention of a 62 bp intron and disrupting RNA splicing, represents the first documented case of intron retention in TCS patients. Additionally, the previously reported mutation c.136 C> G (p.L46V) hinders protein nuclear location, while mutation c.1719del (p.N574TfsTer22) significantly decreases mRNA levels.
CONCLUSIONS: Our research expands the spectrum of TCOF1 mutations and provides evidence clarifying their pathogenic nature. These findings are crucial for genetic counseling and prenatal diagnosis for TCS patients.
RESULTS: We report two novel mutations identified in two TCS families and assess their pathogenicity alongside two previously reported mutations. Both novel mutations, c.2115dupG (p.T706DfsTer52) and c.2142+23_2142+52 del (p.A715VfsTer31), result in truncated proteins lacking nuclear location signals (NLSs), which impedes their entry into the nucleus and reduces mRNA expression level. Notably, the mutation c.2142+23_2142+52 del, leading to the retention of a 62 bp intron and disrupting RNA splicing, represents the first documented case of intron retention in TCS patients. Additionally, the previously reported mutation c.136 C> G (p.L46V) hinders protein nuclear location, while mutation c.1719del (p.N574TfsTer22) significantly decreases mRNA levels.
CONCLUSIONS: Our research expands the spectrum of TCOF1 mutations and provides evidence clarifying their pathogenic nature. These findings are crucial for genetic counseling and prenatal diagnosis for TCS patients.