PDF(Pubmed)
Abstract：
BACKGROUND: Biallelic pathogenic variants in PIP5K1C (MIM #606,102) lead to lethal congenital contractural syndrome 3 (LCCS3, MIM #611,369), a rare autosomal recessive genetic disorder characterized by small gestational age, severe multiple joint contractures and muscle atrophy, early death due to respiratory failure. Currently, 5 individuals with LCCS3 were reported and 5 pathogenic variants in PIP5K1C were identified. Here, we reported the two fetuses in a Chinese pedigree who displayed multiple joint contractures and other congenital anomalies.
METHODS: Trio-based whole-exome sequencing (WES) was performed for the parents and the recent fetus to detect the genetic cause for fetus phenotype.
RESULTS: A novel variant, NM_012398.3: c.949_952dup, p.S318Ifs*28 and a previously reported variant, c.688_689del, p.G230Qfs*114 (ClinVar database) in PIP5K1C, were detected in the individuals, and these variants were inherited from the mother and father, respectively. We described the features of multiple joint contractures in our fetuses, including bilateral talipes equinovarus, stiffness in the limbs, extended knees, persistently closed hands and overlapping fingers, which have not been delineated detailedly in previously reported LCCS3 individuals. Furthermore, novel phenotype, bilateral dilated lateral ventricles, was revealed in one fetus.
CONCLUSIONS: These findings expanded the genetic variant spectrum of PIP5K1C and enriched the clinical features of LCCS3, which will help with the prenatal diagnosis and genetic counseling for this family.
METHODS: Trio-based whole-exome sequencing (WES) was performed for the parents and the recent fetus to detect the genetic cause for fetus phenotype.
RESULTS: A novel variant, NM_012398.3: c.949_952dup, p.S318Ifs*28 and a previously reported variant, c.688_689del, p.G230Qfs*114 (ClinVar database) in PIP5K1C, were detected in the individuals, and these variants were inherited from the mother and father, respectively. We described the features of multiple joint contractures in our fetuses, including bilateral talipes equinovarus, stiffness in the limbs, extended knees, persistently closed hands and overlapping fingers, which have not been delineated detailedly in previously reported LCCS3 individuals. Furthermore, novel phenotype, bilateral dilated lateral ventricles, was revealed in one fetus.
CONCLUSIONS: These findings expanded the genetic variant spectrum of PIP5K1C and enriched the clinical features of LCCS3, which will help with the prenatal diagnosis and genetic counseling for this family.
摘要：
背景：PIP5K1C（MIM＃606,102）的双等位基因致病变异导致致命的先天性挛缩综合征3（LCCS3，MIM＃611,369），一种罕见的常染色体隐性遗传性疾病，其特征是胎龄较小，严重的多发性关节挛缩和肌肉萎缩，呼吸衰竭导致的早期死亡。目前,报告了5名患有LCCS3的个体，并鉴定了PIP5K1C中的5种致病变体。这里,我们报道了中国家系中的两个胎儿，他们表现出多发性关节挛缩和其他先天性异常。
方法：对父母和近期胎儿进行基于三重奏的全外显子组测序（WES），以检测胎儿表型的遗传原因。
结果：一种新的变体，NM_012398.3：c.949_952dup，p.S318Ifs*28和以前报道的变体，c.688_689del,PIP5K1C中的p.G230Qfs*114（ClinVar数据库），在个体中检测到，这些变体是从母亲和父亲那里继承的，分别。我们描述了胎儿多处关节挛缩的特点,包括双侧马蹄内翻足,四肢僵硬，膝盖伸展,持续闭合的手和重叠的手指，在以前报告的LCCS3个体中没有详细描述。此外，新的表型，双侧侧脑室扩张，是在一个胎儿身上发现的.
结论：这些发现扩大了PIP5K1C的遗传变异谱，丰富了LCCS3的临床特征，有助于该家族的产前诊断和遗传咨询。
方法：对父母和近期胎儿进行基于三重奏的全外显子组测序（WES），以检测胎儿表型的遗传原因。
结果：一种新的变体，NM_012398.3：c.949_952dup，p.S318Ifs*28和以前报道的变体，c.688_689del,PIP5K1C中的p.G230Qfs*114（ClinVar数据库），在个体中检测到，这些变体是从母亲和父亲那里继承的，分别。我们描述了胎儿多处关节挛缩的特点,包括双侧马蹄内翻足,四肢僵硬，膝盖伸展,持续闭合的手和重叠的手指，在以前报告的LCCS3个体中没有详细描述。此外，新的表型，双侧侧脑室扩张，是在一个胎儿身上发现的.
结论：这些发现扩大了PIP5K1C的遗传变异谱，丰富了LCCS3的临床特征，有助于该家族的产前诊断和遗传咨询。
