PDF(Pubmed)
Abstract：
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 TCOF1 (c.4369_4373delAAGAA, p.K1457Efs*12). The mutation was not detected in his parents\' peripheral blood DNA samples, suggesting a de novo 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 TCOF1 mutation. Our findings highlight the importance of considering germline mosaicism in sporadic de novo TCOF1 mutations when providing genetic consulting, and prenatal diagnosis is important when the proband\'s parents become pregnant again.
摘要：
TreacherCollins综合征（TCS）是一种罕见的先天性颅面疾病，通常作为常染色体显性遗传。这里,我们报道了一个可能存在TCS生殖系镶嵌的家族。先证者根据典型的临床特征和致病性变异体TCOF1诊断为TCS(c.4369_4373delAAGAA，p.K1457Efs*12)。在他父母的外周血DNA样本中没有检测到这种突变,提示先证者发生了从头突变。然而,一年后,先证者的母亲怀孕了,羊水穿刺显示胎儿携带与先证者相同的突变。产前超声还显示颌面部发育不良伴单侧小耳畸形。这位母亲随后透露了以前的出生史，其中一名婴儿在出生后不久死于呼吸窘迫，显示TCS样表型。大约在同一时间,先证者的父亲被诊断为轻度双侧传导性听力损失。基于阵列数据，我们得出的结论是，父亲可能对TCOF1突变有种系镶嵌。我们的发现强调了在提供遗传咨询时，在零星的从头TCOF1突变中考虑种系镶嵌的重要性。当先证者的父母再次怀孕时，产前诊断很重要。
