RESUMEN
OBJECTIVE: The L1 cell adhesion molecule (L1CAM) gene, encodes the L1 cell adhesion molecule, is involved in the central nervous system development. Its mutations result in L1 syndrome which is associated with brain malformation and nervous developmental delay. CASE REPORT: We presented three fetuses with hydrocephalus and agenesis of the corpus callosum detected by ultrasound, followed by medical exome sequencing (MES) test with L1CAM mutations: two known missense mutation c.551G > A (p. R184Q) and c.1354G > A (p. G452R), and a novel frameshift mutation c.1322delG which causes the early termination of translation (p. G441Afs∗72). By utilizing multiple computational analysis, all the variants were scored to be likely pathogenic. CONCLUSION: Combined use of ultrasound and MES to identify the molecular etiology of fetal anomalies may contribute to expanding our knowledge of the clinical phenotype of L1 syndrome observed in the south Chinese population.
Asunto(s)
Secuenciación del Exoma , Exoma/genética , Feto/anomalías , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Discapacidad Intelectual/diagnóstico , Molécula L1 de Adhesión de Célula Nerviosa/genética , Paraplejía Espástica Hereditaria/diagnóstico , Adulto , Agenesia del Cuerpo Calloso/diagnóstico , Agenesia del Cuerpo Calloso/embriología , Agenesia del Cuerpo Calloso/genética , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/embriología , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/embriología , Hidrocefalia/genética , Discapacidad Intelectual/embriología , Discapacidad Intelectual/genética , Mutación , Fenotipo , Embarazo , Paraplejía Espástica Hereditaria/embriología , Paraplejía Espástica Hereditaria/genética , Ultrasonografía PrenatalRESUMEN
OBJECTIVE: To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service. METHODS: Five cases with secondary findings were reviewed. RESULTS: In Case 1, NIPT revealed a large duplication in chromosome 18p, which was supported by arrayCGH of amniocyte DNA, with final karyotype showing mosaic tetrasomy 18p. In Case 2, a deletion in the proximal long arm of chromosome 18 of maternal origin was suspected and confirmed by arrayCGH of maternal white cell DNA. In Case 3, NIPT was negative for trisomies 21 and 18. In-depth analysis for deletions/duplications was requested when fetal structural anomalies were detected at routine scan. A deletion in the proximal long arm of chromosome 3 was found and confirmed by karyotyping. In Case 4, NIPT correctly predicted confined placental mosaicism with triple trisomy involving chromosomes X, 7 and 21. In Case 5, NIPT correctly detected a previously unknown maternal mosaicism for 45X. CONCLUSION: Non-invasive prenatal testing is able to detect a wide range of fetal, placental and maternal chromosomal abnormalities. This has important implications on patient counseling when an abnormality is detected by NIPT.
Asunto(s)
Aneuploidia , Cromosomas Humanos Par 21/genética , Síndrome de Down/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Diagnóstico Prenatal/métodos , Trisomía/diagnóstico , Adulto , Cromosomas Humanos Par 18 , Cromosomas Humanos X/genética , Servicios de Laboratorio Clínico , ADN/sangre , ADN/genética , Reacciones Falso Negativas , Femenino , Feto/metabolismo , Humanos , EmbarazoRESUMEN
Uniparental disomy (UPD) is an uncommon chromosome condition, but UPD involving chromosome 21 is rarely reported. We reported here a case who had first trimester screening test for Down syndrome, chorionic villus sampling for fetal karyotyping, quantitative fluorescence polymerase chain reaction (QF-PCR), as well as non-invasive prenatal testing (NIPT) by maternal plasma sequencing. There were discordant results between fetal karyotyping and NIPT due to UPD 21combined with confined placental mosaicism of trisomy 21. This demonstrated that it is possible to detect placental mosaicism by NIPT, but further studies are required to confirm its sensitivity. Therefore, all positive NIPT results must be confirmed by conventional invasive test and karyotyping. QF-PCR has the additional benefit in diagnosing UPD.