title: Presymptomatic genetic analysis during pregnancy for vascular type Ehlers-Danlos syndrome.
abstract: The vascular type of Ehlers-Danlos syndrome (EDS), EDS type IV (Online Mendelian Inheritance in Man [MIM] #130050) is characterized by thin, translucent skin, easy bruising, and arterial, intestinal, and/or uterine fragility during pregnancy, which may lead to sudden death. It is an autosomal dominant inherited disorder caused by type III procollagen gene (COL3A1: MIM #120180) mutations. Approximately 50% of the COL3A1 mutations are inherited from an affected parent, and 50% are de novo mutations. Each child of an affected individual has a 50% chance of inheriting the mutation and developing the disorder. Pregnant women with vascular EDS are at an increased risk of uterine and arterial rupture during the peripartum period, with high maternal morbidity and mortality rates. We report the first case of an asymptomatic 35-year-old woman at a risk of complications of vascular EDS who underwent presymptomatic evaluation during pregnancy. The sequencing results of both her brother and mother had a one-base-pair deletion, resulting in Glutamate at position 730 changing to Lysine and causing a frame shift and premature termination codon at 61 amino acids from the mutation position (p. Glu730Lysfs*61) on exon 32 of COL3A1. This deletion caused frameshift, leading to a premature termination codon (TAG) at 181 nucleotides downstream in exon 35, which could not be detected by previous total RNA (ribonucleic acid) method. Thus, she was at risk of complications of vascular EDS, and diagnostic testing was employed at 8 weeks of pregnancy to minimize the risk of developing vascular EDS-related complications. The negative presymptomatic diagnostic result allowed the patient to choose normal delivery at term. Vascular EDS is a serious disorder, with high mortality, especially in high-risk women with vascular EDS during pregnancy. The presymptomatic genetic testing of vascular EDS during pregnancy for a high-risk family can help with the early establishment of preventive measures.
authors: Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan.
authors: Banyar Than
authors: BT
authors: Naing
authors: Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan ; Division of Clinical Genetics, Nippon Medical School Hospital, Tokyo, Japan.
authors: Atsushi
authors: A
authors: Watanabe
authors: Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Tokyo, Japan.
authors: Shinji
authors: S
authors: Tanigaki
authors: Department of Pediatrics, Kyorin University School of Medicine, Tokyo, Japan.
authors: Masae
authors: M
authors: Ono
authors: Department of Obstetrics and Gynecology, Kyorin University School of Medicine, Tokyo, Japan.
authors: Mitsutoshi
authors: M
authors: Iwashita
authors: Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan ; Division of Clinical Genetics, Nippon Medical School Hospital, Tokyo, Japan.
authors: Takashi
authors: T
authors: Shimada
keywords: testing; type III procollagen gene (COL3A1); vascular EDS