Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Radiology, Peking Union Medical College Hospital, Beijing, China.
Sci Prog. 2024 Apr-Jun;107(2):368504241242278. doi: 10.1177/00368504241242278.
Treacher Collins syndrome (TCS) is a rare congenital craniofacial disorder, typically inherited as an autosomal dominant condition. Here, we report on a family in which germline mosaicism for TCS was likely present. The proband was diagnosed with TCS based on the typical clinical features and a pathogenic variant (c.4369_4373delAAGAA, p.K1457Efs*12). The mutation was not detected in his parents' peripheral blood DNA samples, suggesting a mutation had occurred in the proband. However, a year later, the proband's mother became pregnant, and the amniotic fluid puncture revealed that the fetus carried the same mutation as the proband. Prenatal ultrasound also indicated a maxillofacial dysplasia with unilateral microtia. The mother then disclosed a previous birth history in which a baby had died of respiratory distress shortly after birth, displaying a TCS-like phenotype. Around the same time, the proband's father was diagnosed with mild bilateral conductive hearing loss. Based on array data, we concluded that the father may have had germline mosaicism for mutation. Our findings highlight the importance of considering germline mosaicism in sporadic mutations when providing genetic consulting, and prenatal diagnosis is important when the proband's parents become pregnant again.
特雷彻·柯林斯综合征（TCS）是一种罕见的先天性颅面畸形，通常作为常染色体显性遗传疾病遗传。在这里，我们报告了一个可能存在 TCS 种系镶嵌的家族。先证者根据典型的临床特征和致病性变异（c.4369_4373delAAGAA，p.K1457Efs*12）被诊断为 TCS。该突变未在其父母的外周血 DNA 样本中检测到，提示先证者发生了突变。然而，一年后，先证者的母亲再次怀孕，羊水穿刺显示胎儿携带与先证者相同的突变。产前超声还显示单侧小耳伴颌面发育不良。母亲随后透露了之前的分娩史，一个婴儿出生后不久因呼吸窘迫而死亡，表现出 TCS 样表型。大约在同一时间，先证者的父亲被诊断出患有轻度双侧传导性听力损失。基于阵列数据，我们得出结论，父亲可能存在 突变的种系镶嵌。我们的发现强调了在提供遗传咨询时，对于散发性 突变应考虑种系镶嵌的重要性，并且当先证者的父母再次怀孕时，产前诊断很重要。
