Prenatal diagnosis of a 5q35.3 microduplication involving part of the ADAMTS2 locus: a likely benign variant without apparent phenotypic abnormality

Abstract

Rationale: Chromosomal duplications are associated with a series of genetic disorders. However, chromosome 5q duplications, especially pure 5q35.3 microduplications, have rarely been reported in the literature. Clinical phenotypes usually depend on the region of chromosome duplicated, its size, and loci. Patient concerns: From 2011 to 2017, prenatal amniotic fluid samples were obtained from 6 pregnant women diagnosed with pure 5q35.3 microduplications following different prenatal indications at our center. We followed up the children of these pregnancies and determined their postnatal health conditions. Diagnoses: Cytogenetic studies delineated that all patients had normal karyotypes, except for patient 6 who had 46,XX,inv(9)(p11q13). Single-nucleotide polymorphism array results showed 177–269 kb duplications of 5q35.3 (chr5:178728830–178997692) in these cases. All shared similar localization of ADAMTS2. Interventions: All pregnant women chose to continue the pregnancies. Follow-up analysis showed that the children presented normal physical and growth developments. Outcomes: We described six prenatal cases with similar 5q35.3 duplications involving part of the ADAMTS2 locus with no apparent postnatal phenotypic abnormalities. Lessons: Our research revealed that partial microduplication of ADAMTS2 (chr5:178728830–178997692) might be benign and not correlate with disorders. And there might exist phenotypic diversities of 5q35.3 duplications.

Clinical characterization of chromosome 5q21.1–21.3 microduplication: A case report

“…However, microduplication of the long arm of chromosome 5 is extremely rare. Although microduplications of 5q35.2–q35.3 have been reported [ 4 , 6 , 8 ], chromosome 5q21.1–21.3 microduplication has not been clinically characterized. We report the prenatal diagnosis of a fetus with a 4.7 Mb microduplication of chromosome 5q21.1–q21.3, inherited from his mother.…”

“…Amniotic fluid cells were obtained through amniocentesis after obtaining written informed consent, collected by centrifugation, inoculated in flasks in accordance with laboratory standards, and cultured in CO 2 incubators for 10 days. Chromosome analysis using GTG staining was performed similar to our previous study [ 4 ]. The karyotype was described in accordance with the International System for Human Cytogenetic Nomenclature (ISCN 2013) [ 10 ].…”

“…Through prenatal diagnosis of CMA, some microdeletions or microduplications can be detected before birth to avoid unnecessary abortions or birth defects [ 3 ]. The clinical features of some chromosome 5 microduplications have been described previously [ 4 , 5 , 6 , 7 , 8 ]. Jamsheer et al [ 8 ] presented a case of bilateral radial agenesis with absent thumbs, complex heart defect, short stature, and facial dysmorphism in a 9.5-year-old patient with pure distal microduplication of 5q35.2–5q35.3.…”