Double Autosomal/Gonosomal Mosaic Trisomy 47,XXX/47,XX,+14 in a Newborn with Multiple Congenital Anomalies

Abstract

Chromosomal trisomies are the most frequent major chromosomal anomalies in humans and can be present in a mosaic or a non-mosaic constitution. We report the first case of a newborn girl presenting with multiple congenital anomalies and a double mosaic trisomy involving chromosome 14 and the X chromosome detected by array CGH. Karyotype analysis revealed a double mosaic with 2 independent abnormal cell lines and the absence of 46,XX and 48,XXX,+14 cell lineages. The patient showed most of the clinical characteristics of mosaic trisomy 14. Analysis of autosomal DNA markers in the proband's blood sample did not support the presence of chimerism. Further analysis of chromosome X DNA markers suggests that the extra X chromosome most probably arose as a consequence of nondisjunction in meiosis II in the maternal lineage.

Uniparental disomy: expanding the clinical and molecular phenotypes of whole chromosomes

“…These patients are believed to have specific phenotypes of T14 and TS (Garza-Mayén et al, 2021;Lindgren et al, 2021). According to these reports, mosaic T14 cases may display phenotypes of frontal bossing, ocular hypertelorism, widening of the posterior cranial fossa, micrognathia, abnormal cardiac structure, strephenopodia in early pregnancy, IUGR, hydramnios/ oligohydramnios, cleft palate, high arched jaw, microcephaly, pericardial effusion, cardiac malformation, omphalocele, clenched fist and syndactyly in the late trimester (Massara et al, 2019), some of which are partially consistent with our UPD14 case. However, the final phenotypes are dependent on the percentage of mosaicism ratio and tissue distribution of the mosaic cells.…”

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

“…Among the 93 patients selected for array-CGH (array comparative genomic hybridization) analysis, 89 samples were studied with the ISCA v2 8×60K platform and 4 with ISCA 4×180K (Agilent, Santa Clara, CA, USA) platform, as previously described [ 30 , 31 ]. For the categorization of the CNVs, the American College of Medical Genetic and Genomics (ACMG) and ClinGen technical standards for interpretation and reporting of constitutional CNVs [ 32 ] were followed.…”

“… 1 : These patients were also analyzed by array-CGH (refer to Table 3 for details). 2 : Described in Massara et al, 2019 [ 31 ]; 3 : Confirmed by FISH. …”

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

“…Patients were studied with the ISCA v2 8×60K (Agilent, Santa Clara, CA, USA) platform as previously described [16,17]. In some cases, familial samples were analyzed for a full interpretation of the proband's array results.…”