{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:11:20Z","timestamp":1760238680768,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,22]],"date-time":"2020-08-22T00:00:00Z","timestamp":1598054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology, Executive Yuan, Taiwan","award":["MOST 107-2314-B-371-009-MY3"],"award-info":[{"award-number":["MOST 107-2314-B-371-009-MY3"]}]},{"name":"Changhua Christian Hospital, Taiwan","award":["105-CCH-IRP-102"],"award-info":[{"award-number":["105-CCH-IRP-102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Chromosome microarray analysis has been used for prenatal detection of copy number variations (CNVs) and genetic counseling of CNVs has been greatly improved after the accumulation of knowledge from postnatal outcomes in terms of the genotype-phenotype correlation. However, a significant number of CNVs are still regarded as variants of unknown significance (VUS). CNVs at the chromosome X (X-CNVs) represent a unique group of genetic changes in genetic counseling; X-CNVs are similar to X-linked recessive monogenic disorders in that the prognosis in males is expected to be poor. Trio analysis is typically advised to patients with X-CNVs but such an approach may be inadequate in prenatal settings since the clinical relevance is sometimes uninformative, particularly for the maternally inherited X-CNVs in male fetuses. Here, we reported four healthy women whose male fetuses were found to have X-CNVs inherited from the mothers. The X-CNVs were initially recognized as VUS or likely pathogenic in males according to the publicly available information. After extending genetic analyses to male relatives of the maternal lineages, however, the relevance of the X-CNVs was reconsidered to be likely benign. The results highlight that an extended analysis to include more relatives, in addition to the parents, provides further information for genetic counseling when X-CNVs are encountered in prenatal settings.<\/jats:p>","DOI":"10.3390\/genes11090979","type":"journal-article","created":{"date-parts":[[2020,8,23]],"date-time":"2020-08-23T21:28:06Z","timestamp":1598218086000},"page":"979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Relevance of Copy Number Variation at Chromosome X in Male Fetuses Inherited from the Mother May Be Ascertained by Including Male Relatives from the Maternal Lineage in Addition to Trio Analyses"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5076-2917","authenticated-orcid":false,"given":"Ming","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"Research Department, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan"},{"name":"Department of Medical Genetics, National Taiwan University Hospital, Taipei 10041, Taiwan"},{"name":"Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 10041, Taiwan"},{"name":"Department of Biomedical Science, Dayeh University, Changhua 51591, Taiwan"},{"name":"Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Ju","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"Ph.D. Programs in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Hui","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tien-Hsiung","family":"Ku","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Changhua Christian Hospital, Changhua 50006, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwo-Chin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"},{"name":"Research Department, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua 50046, Taiwan"},{"name":"Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan 32023, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1056\/NEJMoa1203382","article-title":"Chromosomal microarray versus karyotyping for prenatal diagnosis","volume":"367","author":"Wapner","year":"2012","journal-title":"N. 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