Abstract：
UNASSIGNED: VATER/VACTERL-like association is associated with adverse pregnancy outcomes. Genetic evidence of this disorder is sporadic. In this study, we aimed to provide genetic insights to improve the diagnosis of VACTERL.
UNASSIGNED: We have described a Chinese family in which four members were affected by renal defects or agenesis, anal atresia, and anovaginal fistula, which is consistent with the diagnosis of a VACTERL-like association. Pedigree and genetic analyses were conducted using genome and exome sequencing.
UNASSIGNED: Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals, harboring a 196-380 kb microdeletion on Xq27.1, which was identified by familial exome sequencing. Genome sequencing was performed on the affected male, confirming a -196 kb microdeletion in Xq27.1, which included a 28% loss of the CDR-1 gene. Four family members were included in the co-segregation analysis, and only VACTERL-like cases with microdeletions were reported in X27.1.
UNASSIGNED: These results suggest that the 196-380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association. However, further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.
UNASSIGNED: We have described a Chinese family in which four members were affected by renal defects or agenesis, anal atresia, and anovaginal fistula, which is consistent with the diagnosis of a VACTERL-like association. Pedigree and genetic analyses were conducted using genome and exome sequencing.
UNASSIGNED: Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals, harboring a 196-380 kb microdeletion on Xq27.1, which was identified by familial exome sequencing. Genome sequencing was performed on the affected male, confirming a -196 kb microdeletion in Xq27.1, which included a 28% loss of the CDR-1 gene. Four family members were included in the co-segregation analysis, and only VACTERL-like cases with microdeletions were reported in X27.1.
UNASSIGNED: These results suggest that the 196-380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association. However, further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.
摘要：
■VATER/VACTERL样关联与不良妊娠结局相关。这种疾病的遗传证据是零星的。在这项研究中,我们旨在提供遗传学见解,以改善VACTERL的诊断.
■我们描述了一个中国家庭，其中四个成员受到肾脏缺陷或发育不全的影响，肛门闭锁,和阴道瘘,这与VACTERL样关联的诊断一致。使用基因组和外显子组测序进行谱系和遗传分析。
■分离分析显示，在两个活着的受影响个体中存在隐性X连锁微缺失，在Xq27.1上有196-380kb的微缺失，通过家族外显子组测序鉴定。对受影响的男性进行基因组测序，确认Xq27.1中的〜196kb微缺失,其包括CDR-1基因的28%损失。四个家庭成员被包括在共同隔离分析中，X27.1报道了仅有VACTERL样的微缺失病例。
■这些结果表明，Xq27.1中的196-380kb微缺失可能是VATER/VACTERL样关联的可能原因。然而,需要进一步的遗传和功能分析,以确认或排除遗传背景是VACTERL关联的最终原因.
■我们描述了一个中国家庭，其中四个成员受到肾脏缺陷或发育不全的影响，肛门闭锁,和阴道瘘,这与VACTERL样关联的诊断一致。使用基因组和外显子组测序进行谱系和遗传分析。
■分离分析显示，在两个活着的受影响个体中存在隐性X连锁微缺失，在Xq27.1上有196-380kb的微缺失，通过家族外显子组测序鉴定。对受影响的男性进行基因组测序，确认Xq27.1中的〜196kb微缺失,其包括CDR-1基因的28%损失。四个家庭成员被包括在共同隔离分析中，X27.1报道了仅有VACTERL样的微缺失病例。
■这些结果表明，Xq27.1中的196-380kb微缺失可能是VATER/VACTERL样关联的可能原因。然而,需要进一步的遗传和功能分析,以确认或排除遗传背景是VACTERL关联的最终原因.
