TY - JOUR

T1 - Prenatal diagnosis of small supernumerary marker chromosome 10 by array-based comparative genomic hybridization and microdissected chromosome sequencing

AU - Lebedev, Igor N.

AU - Karamysheva, Tatyana V.

AU - Elisaphenko, Eugeny A.

AU - Makunin, Alexey I.

AU - Zhigalina, Daria I.

AU - Lopatkina, Maria E.

AU - Drozdov, Gleb V.

AU - Cheremnykh, Aleksander D.

AU - Torkhova, Natalia B.

AU - Seitova, Gulnara N.

AU - Vasilyev, Stanislav A.

AU - Kashevarova, Anna A.

AU - Nazarenko, Ludmila P.

AU - Rubtsov, Nikolay B.

N1 - Funding Information: Funding: This study was supported by the Russian Science Foundation (#21-65-00017), https:// rscf.ru/project/21-65-00017/ in the prenatal diagnosis, clinical investigations, aCGH and real-time PCR analyses. Chromosomal microdissection and FISH analyses were supported by the Russian Foundation for Basic Research (#19-015-00084a). DNA sequencing and data analysis were performed with support from the State Budget of ICG and by the Ministry of Science and Higher Education of the Russian Federation via IC&G SB RAS (#0259-2021-0011). A.I.M was supported by the Wellcome Trust grant 206194. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/8

Y1 - 2021/8

N2 - Interpreting the clinical significance of small supernumerary marker chromosomes (sSMCs) in prenatal diagnosis is still an urgent problem in genetic counselling regarding the fate of a pregnancy. We present a case of prenatal diagnosis of mosaic sSMC(10) in a foetus with a normal phenotype. Comprehensive cytogenomic analyses by array-based comparative genomic hybridization (aCGH), sSMC microdissection with next-generation sequencing (NGS) of microdissected library, fluorescence in situ hybridization (FISH) with locus-specific and telomere-specific DNA probes and quantitative real-time PCR revealed that sSMC(10) had a ring structure and was derived from the pericentromeric region of chromosome 10 with involvement of the 10p11.21-p11.1 and 10q11.21-q11.23 at 1.243 Mb and 7.173 Mb in size, respectively. We observed a difference in the length of sSMC(10) between NGS data of the DNA library derived from a single copy of sSMC(10), and aCGH results that may indicate instability and structural mosaicism for ring chromosomes in foetal cells. The presence of a 9 Mb euchromatin region in the analysed sSMC(10) did not lead to clinical manifestations, and a healthy girl was born at term. We suggest that the ring structure of sSMCs could influence sSMC manifestations and should be taken into account in genetic counselling during prenatal diagnosis.

AB - Interpreting the clinical significance of small supernumerary marker chromosomes (sSMCs) in prenatal diagnosis is still an urgent problem in genetic counselling regarding the fate of a pregnancy. We present a case of prenatal diagnosis of mosaic sSMC(10) in a foetus with a normal phenotype. Comprehensive cytogenomic analyses by array-based comparative genomic hybridization (aCGH), sSMC microdissection with next-generation sequencing (NGS) of microdissected library, fluorescence in situ hybridization (FISH) with locus-specific and telomere-specific DNA probes and quantitative real-time PCR revealed that sSMC(10) had a ring structure and was derived from the pericentromeric region of chromosome 10 with involvement of the 10p11.21-p11.1 and 10q11.21-q11.23 at 1.243 Mb and 7.173 Mb in size, respectively. We observed a difference in the length of sSMC(10) between NGS data of the DNA library derived from a single copy of sSMC(10), and aCGH results that may indicate instability and structural mosaicism for ring chromosomes in foetal cells. The presence of a 9 Mb euchromatin region in the analysed sSMC(10) did not lead to clinical manifestations, and a healthy girl was born at term. We suggest that the ring structure of sSMCs could influence sSMC manifestations and should be taken into account in genetic counselling during prenatal diagnosis.

KW - Array-based comparative genomic hybridization

KW - Chromosomal microdissection

KW - Mosaicism

KW - Prenatal diagnosis

KW - Ring chromosome

KW - Single-copy chromosome sequencing

KW - Small supernumerary marker chromosome

UR - http://www.scopus.com/inward/record.url?scp=85113373363&partnerID=8YFLogxK

U2 - 10.3390/biomedicines9081030

DO - 10.3390/biomedicines9081030

M3 - Article

C2 - 34440234

AN - SCOPUS:85113373363

VL - 9

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 8

M1 - 1030

ER -