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

被引:3
作者
Kashevarova, Anna A. [1 ]
Nikitina, Tatyana, V [1 ]
Mikhailik, Larisa, I [2 ]
Belyaeva, Elena O. [1 ]
Vasilyev, Stanislav A. [1 ]
Lopatkina, Mariya E. [1 ]
Fedotov, Dmitry A. [1 ]
Fonova, Elizaveta A. [1 ]
Zarubin, Aleksei A. [1 ]
Sivtsev, Aleksei A. [1 ]
Skryabin, Nikolay A. [1 ]
Nazarenko, Lyudmila P. [1 ]
Lebedev, Igor N. [1 ]
机构
[1] Tomsk Natl Res Med Ctr NRMC, Res Inst Med Genet, Ushaika St 10, Tomsk 634050, Russia
[2] Reg Clin Ctr Specialized Med Care, Vladivostok 690091, Russia
基金
俄罗斯科学基金会;
关键词
ring chromosome 8; invdupdel(8p); Birk-Barel syndrome; KCNK9; imprinting; RING CHROMOSOME-8; SHORT ARM; INVERTED DUPLICATION; MOLECULAR CHARACTERIZATION; INVERSION; DELETIONS; 8P; GENE; BOY;
D O I
10.3390/genes11121473
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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收藏
页码:1 / 18
页数:18
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