Cao Peixuan, Zhu Xiangyu, Gu Leilei, Li Jie
Prenatal Diagnosis Center, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Jun 10;39(6):611-615. doi: 10.3760/cma.j.cn511374-20210427-00368.
To detect pathological variant in a Chinese pedigree affected with oral-facial-digital syndrome type 1 (OFD1).
Whole-exome sequencing was used to scan the whole exome of the proband. Potential variant of the OFD1 gene was also detected in all members of the pedigree and 100 healthy controls by Sanger sequencing. X chromosome inactivation analysis was performed. With the determination of the genotype, prenatal diagnosis was carried out by amniotic fluid sampling.
A c.1189_1192delAATC (p. Q398Lfs*2) variant was identified in the OFD1 gene of the proband, other patients from this pedigree, as well as the fetus. The same variant was not found among healthy members from this pedigree and the 100 healthy controls. X chromosome inactivation analysis identifies the pregnant woman and her younger sister both had a non-random inactivation, other women patients had a random inactivation.
The c.1189_1192delAATC (p. Q398Lfs*2) variant of the OFD1 gene probably underlies the pathogenesis in this case. The new variant has enriched pathological spectrum of the OFD1 gene. The reason of intrafamilial clinical variability still need to be further confirmed.
检测一个患1型口面指综合征（OFD1）的中国家系中的致病变异。
采用全外显子组测序对先证者的整个外显子组进行扫描。通过桑格测序在该家系所有成员及100名健康对照中检测OFD1基因的潜在变异。进行X染色体失活分析。在确定基因型后，通过羊水取样进行产前诊断。
在先证者、该家系的其他患者以及胎儿的OFD1基因中鉴定出一个c.1189_1192delAATC（p.Q398Lfs*2）变异。在该家系的健康成员及100名健康对照中未发现相同变异。X染色体失活分析表明，该孕妇及其妹妹均存在非随机失活，其他女性患者存在随机失活。
OFD1基因的c.1189_1192delAATC（p.Q398Lfs*2）变异可能是该病例发病机制的基础。该新变异丰富了OFD1基因的病理谱。家族内临床变异性的原因仍需进一步证实。
