Rogers Alice, De Jong Lucas, Waters Wendy, Rawlings Lesley H, Simons Keryn, Gao Song, Soubrier Julien, Kenyon Rosalie, Lin Ming, King Rob, Lawrence David M, Muller Peter, Leblanc Shannon, McGregor Lesley, Sallevelt Suzanne C E H, Liebelt Jan, Hardy Tristan S E, Fletcher Janice M, Scott Hamish S, Kulkarni Abhi, Barnett Christopher P, Kassahn Karin S
Paediatric and Reproductive Genetics Unit, Women's and Children's Hospital, Adelaide, South Australia, Australia.
Technology Advancement Unit, Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia.
Aust N Z J Obstet Gynaecol. 2024 Oct;64(5):467-474. doi: 10.1111/ajo.13814. Epub 2024 Apr 5.
Trio exome sequencing can be used to investigate congenital abnormalities identified on pregnancy ultrasound, but its use in an Australian context has not been assessed.
Assess clinical outcomes and changes in management after expedited genomic testing in the prenatal period to guide the development of a model for widespread implementation.
Forty-three prospective referrals for whole exome sequencing, including 40 trios (parents and pregnancy), two singletons and one duo were assessed in a tertiary hospital setting with access to a state-wide pathology laboratory. Diagnostic yield, turn-around time (TAT), gestational age at reporting, pregnancy outcome, change in management and future pregnancy status were assessed for each family.
A clinically significant genomic diagnosis was made in 15/43 pregnancies (35%), with an average TAT of 12 days. Gestational age at time of report ranged from 16 + 5 to 31 + 6 weeks (median 21 + 3 weeks). Molecular diagnoses included neuromuscular and skeletal disorders, RASopathies and a range of other rare Mendelian disorders. The majority of families actively used the results in pregnancy decision making as well as in management of future pregnancies.
Rapid second trimester prenatal genomic testing can be successfully delivered to investigate structural abnormalities in pregnancy, providing crucial guidance for current and future pregnancy management. The time-sensitive nature of this testing requires close laboratory and clinical collaboration to ensure appropriate referral and result communication. We found the establishment of a prenatal coordinator role and dedicated reporting team to be important facilitators. We propose this as a model for genomic testing in other prenatal services.
三联体全外显子组测序可用于调查孕期超声检查发现的先天性异常，但尚未在澳大利亚的背景下对其应用进行评估。
评估孕期快速基因组检测后的临床结果和管理变化，以指导广泛实施的模型的开发。
在一家可使用全州范围病理实验室的三级医院环境中，对43例全外显子组测序的前瞻性转诊病例进行了评估，其中包括40个三联体（父母和胎儿）、2个单胎和1个双亲样本。对每个家庭评估诊断率、周转时间（TAT）、报告时的孕周、妊娠结局、管理变化和未来妊娠状况。
15/43例妊娠（35%）做出了具有临床意义的基因组诊断，平均TAT为12天。报告时的孕周范围为16⁺⁵至31⁺⁶周（中位数为21⁺³周）。分子诊断包括神经肌肉和骨骼疾病、RAS病以及一系列其他罕见的孟德尔疾病。大多数家庭在妊娠决策以及未来妊娠管理中积极使用检测结果。
孕中期快速产前基因组检测可成功用于调查孕期结构异常，为当前和未来的妊娠管理提供关键指导。这种检测的时间敏感性要求实验室和临床密切合作，以确保适当的转诊和结果沟通。我们发现设立产前协调员角色和专门的报告团队是重要的促进因素。我们提议将此作为其他产前服务中基因组检测的模式。
