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Article

46,XY,r(8)/45,XY,−8 Mosaicism as a Possible Mechanism of the Imprinted Birk-Barel Syndrome: A Case Study

1
Research Institute of Medical Genetics, Tomsk National Research Medical Center (NRMC), Ushaika Street 10, 634050 Tomsk, Russia
2
Regional Clinical Center for Specialized Medical Care, 690091 Vladivostok, Russia
*
Author to whom correspondence should be addressed.
Genes 2020, 11(12), 1473; https://doi.org/10.3390/genes11121473
Received: 19 November 2020 / Revised: 25 November 2020 / Accepted: 7 December 2020 / Published: 9 December 2020
(This article belongs to the Special Issue Causes and Consequences of Chromosomal Aberrations)
Ring chromosome 8 (r(8)) is one of the least frequent ring chromosomes. Usually, maternal chromosome 8 forms a ring, which can be lost from cells due to mitotic instability. The 8q24 region contains the imprinted KCNK9 gene, which is expressed from the maternal allele. Heterozygous KCNK9 mutations are associated with the imprinting disorder Birk-Barel syndrome. Here, we report a 2.5-year-old boy with developmental delay, microcephaly, dysmorphic features, diffuse muscle hypotonia, feeding problems, motor alalia and noncoarse neurogenic type of disturbance of muscle electrogenesis, partially overlapping with Birk-Barel syndrome phenotype. Cytogenetic analysis of lymphocytes revealed his karyotype to be 46,XY,r(8)(p23q24.3)[27]/45,XY,−8[3]. A de novo 7.9 Mb terminal 8p23.3p23.1 deletion, a 27.1 Mb 8p23.1p11.22 duplication, and a 4.4 Mb intact segment with a normal copy number located between them, as well as a 154-kb maternal LINGO2 gene deletion (9p21.2) with unknown clinical significance were identified by aCGH + SNP array. These aberrations were confirmed by real-time PCR. According to FISH analysis, the 8p23.1-p11.22 duplication was inverted. The ring chromosome originated from maternal chromosome 8. Targeted massive parallel sequencing did not reveal the KCNK9 mutations associated with Birk-Barel syndrome. Our data allow to assume that autosomal monosomy with inactive allele of imprinted gene arising from the loss of a ring chromosome in some somatic cells may be an etiological mechanism of mosaic imprinting disorders, presumably with less severe phenotype. View Full-Text
Keywords: ring chromosome 8; invdupdel(8p); Birk-Barel syndrome; KCNK9; imprinting ring chromosome 8; invdupdel(8p); Birk-Barel syndrome; KCNK9; imprinting
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MDPI and ACS Style

Kashevarova, A.A.; Nikitina, T.V.; Mikhailik, L.I.; Belyaeva, E.O.; Vasilyev, S.A.; Lopatkina, M.E.; Fedotov, D.A.; Fonova, E.A.; Zarubin, A.A.; Sivtsev, A.A.; Skryabin, N.A.; Nazarenko, L.P.; Lebedev, I.N. 46,XY,r(8)/45,XY,−8 Mosaicism as a Possible Mechanism of the Imprinted Birk-Barel Syndrome: A Case Study. Genes 2020, 11, 1473. https://doi.org/10.3390/genes11121473

AMA Style

Kashevarova AA, Nikitina TV, Mikhailik LI, Belyaeva EO, Vasilyev SA, Lopatkina ME, Fedotov DA, Fonova EA, Zarubin AA, Sivtsev AA, Skryabin NA, Nazarenko LP, Lebedev IN. 46,XY,r(8)/45,XY,−8 Mosaicism as a Possible Mechanism of the Imprinted Birk-Barel Syndrome: A Case Study. Genes. 2020; 11(12):1473. https://doi.org/10.3390/genes11121473

Chicago/Turabian Style

Kashevarova, Anna A., Tatyana V. Nikitina, Larisa I. Mikhailik, Elena O. Belyaeva, Stanislav A. Vasilyev, Mariya E. Lopatkina, Dmitry A. Fedotov, Elizaveta A. Fonova, Aleksei A. Zarubin, Aleksei A. Sivtsev, Nikolay A. Skryabin, Lyudmila P. Nazarenko, and Igor N. Lebedev. 2020. "46,XY,r(8)/45,XY,−8 Mosaicism as a Possible Mechanism of the Imprinted Birk-Barel Syndrome: A Case Study" Genes 11, no. 12: 1473. https://doi.org/10.3390/genes11121473

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