Matthew Hoi Kin Chau1, Doris Yuk Man Lam2, Xiaofan Zhu1, Yvonne Ka Yin Kwok3, Yuen Ha Ting1, Wan Pang Chan4, Mengmeng Shi1, Sunny Wai Hung Cheung2, Tze Kin Lau3,5, Yves Ville6, Tak Yeung Leung1,7,8, Kwong Wai Choy1,7,8. 1. Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China. 2. NIPT Department, NGS Lab, Xcelom Limited, Hong Kong, China. 3. Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Shatin, Hong Kong, China. 4. Obstetrics & Gynaecology Centre, Hong Kong Sanatorium & Hospital, Hong Kong, China. 5. Fetal Medicine Centre, Paramount Medical Centre, Hong Kong, China. 6. EA 73-28, Faculté de Médecine de l'Université René Descartes, Paris, France. 7. Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China. 8. The Chinese University of Hong Kong-Baylor College of Medicine Joint Center for Medical Genetics, The Chinese University of Hong Kong, Hong Kong, China.
Abstract
OBJECTIVE: To report genome-wide cell-free DNA (cfDNA) screening facilitating the diagnosis of Pallister-Killian syndrome (PKS). METHODS: This is a retrospective cohort analysis of positive genome-wide cfDNA screening results showing increased signal from chromosome 12 and the detection of PKS. The genome-wide cfDNA screening results and the subsequent investigations were reviewed. RESULTS: Three singleton pregnancies (3/29007) from 2016 to 2017 yielded positive results indicating large gains on the entire p-arm of chromosome 12. In two cases, multiple structural abnormalities were detected by prenatal ultrasound and the couples opted for termination of pregnancy. Chromosomal microarray performed on fetal skin tissues of the two abortuses detected mosaic tetrasomy 12p, consistent with PKS. In the third case, karyotype and chromosomal microarray performed on an amniotic fluid sample also showed mosaic tetrasomy 12p. In each of the three cases, genome-wide cfDNA screening revealed a large gain on chromosome 12p; subsequent prenatal or postnatal diagnostic testing confirmed the diagnosis of PKS. CONCLUSION: We report the ability of genome-wide cfDNA screening to provide early suspicion and facilitate the subsequent genetic diagnosis of PKS. As genome-wide cfDNA screening becomes increasingly available, incidental diagnosis of partial aneuploidies is expected to increase.
OBJECTIVE: To report genome-wide cell-free DNA (cfDNA) screening facilitating the diagnosis of Pallister-Killian syndrome (PKS). METHODS: This is a retrospective cohort analysis of positive genome-wide cfDNA screening results showing increased signal from chromosome 12 and the detection of PKS. The genome-wide cfDNA screening results and the subsequent investigations were reviewed. RESULTS: Three singleton pregnancies (3/29007) from 2016 to 2017 yielded positive results indicating large gains on the entire p-arm of chromosome 12. In two cases, multiple structural abnormalities were detected by prenatal ultrasound and the couples opted for termination of pregnancy. Chromosomal microarray performed on fetal skin tissues of the two abortuses detected mosaic tetrasomy 12p, consistent with PKS. In the third case, karyotype and chromosomal microarray performed on an amniotic fluid sample also showed mosaic tetrasomy 12p. In each of the three cases, genome-wide cfDNA screening revealed a large gain on chromosome 12p; subsequent prenatal or postnatal diagnostic testing confirmed the diagnosis of PKS. CONCLUSION: We report the ability of genome-wide cfDNA screening to provide early suspicion and facilitate the subsequent genetic diagnosis of PKS. As genome-wide cfDNA screening becomes increasingly available, incidental diagnosis of partial aneuploidies is expected to increase.