Publication
15q11.2q13.1 interstitial gain in a fetus with an increased risk for T21: When classification and clinical outcome are divergent
| dc.contributor.author | Serafim, Sílvia | |
| dc.contributor.author | Pedro, Sónia | |
| dc.contributor.author | Marques, Bárbara | |
| dc.contributor.author | Tarelho, Ana | |
| dc.contributor.author | Viegas, Mónica | |
| dc.contributor.author | Simão, Laurentino | |
| dc.contributor.author | Ferreira, Cristina | |
| dc.contributor.author | Carvalho, Inês | |
| dc.contributor.author | Cohen, Álvaro | |
| dc.contributor.author | Correia, Hildeberto | |
| dc.date.accessioned | 2024-01-12T14:16:13Z | |
| dc.date.available | 2024-01-12T14:16:13Z | |
| dc.date.issued | 2023-11-23 | |
| dc.description.abstract | Introduction: Copy number variants (CNV) of the 15q11.2q13.1 region are associated to recurrent microdeletion/microduplication syndromes in which the phenotype is dependent on the parental origin of the CNV. We report the case of a fetus from a healthy 39-year-old G6P3A2 woman, with an increased risk for trisomy 21 in the 1st trimester prenatal screening. Chromosomal microarray analysis (CMA) was requested and revealed a pathogenic duplication in which the outcome was dependent of the parental origin of the affected allele. Methods: DNA was extracted from a chorionic villus sample and CMA was performed using Cytoscan™ 750K. Parental follow-up studies to assess the origin of the CNV were performed. Results: The CMA profile revealed a male fetus with a 4,89 Mb interstitial gain in 15q11.2q13.1. CMA of the parents showed that the duplication was paternally inherited. Discussion: The detected CNV is a recurrent known microduplication and according to the American College of Medical Genetics and Genomics guidelines is classified as pathogenic. However the phenotype is dependent on the parental origin of the duplication. When it arises in the maternally allele it has a severe outcome with hypotonia, cognitive deficit, seizures, among others. If the CNV occurs in the paternal allele although some patients might show developmental delays and behavioral disturbances most cases are rarely symptomatic. In this case, CMA of both parents showed that the CNV identified in the fetus was paternally inherited. Although the CMA result did not explained the increased risk for T21 after determining the duplication had been inherited from the father it allowed the prediction of the most likely resulting phenotype for the fetus as a milder or even asymptomatic. Follow-up ultrasounds at gestation age of 17w+6d and echocardiogram at 21w+3d showed no structural abnormalities. The baby was born at 37w+5d with an Apgar index of 10/10/10, with no dysmorphic features or malformations, and a normal physical exam. This case illustrates that although the use of genetic tools using artificial intelligence and following determined guidelines can be helpful for the purpose of consistency and standardization on the classification we always need careful evaluation from a clinical laboratory geneticist on the context of each case. Additionally it also shows how critical parental testing can be, not only to assess recurrence risk but to provide the best possible tool to ascertain the outcoming phenotype and allow the best choices to the couple after genetic counselling. | pt_PT |
| dc.description.version | N/A | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/8894 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.subject | Prenatal Diagnosis | pt_PT |
| dc.subject | 15q11.2q13.1 gain | pt_PT |
| dc.subject | CNV Classification | pt_PT |
| dc.subject | Doenças Genética | pt_PT |
| dc.title | 15q11.2q13.1 interstitial gain in a fetus with an increased risk for T21: When classification and clinical outcome are divergent | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Lisboa, Portugal | pt_PT |
| oaire.citation.title | 27th Annual Meeting of the Portuguese Society of Human Genetics, 23-25 novembro 2023 | pt_PT |
| rcaap.rights | restrictedAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |