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Abstract：
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.
摘要：
环染色体8(r(8))是频率最低的环染色体之一。通常,母系8号染色体形成一个环，由于有丝分裂不稳定，可能会从细胞中丢失。8q24区域含有印迹的KCNK9基因，从母体等位基因表达。杂合KCNK9突变与印迹障碍Birk-Barel综合征相关这里,我们报告了一个发育迟缓的2.5岁男孩，小头畸形,变形特征，弥漫性肌张力减退,喂养问题，运动性alalalia和非粗糙神经源性肌肉电发生障碍类型，与Birk-Barel综合征表型部分重叠。淋巴细胞的细胞遗传学分析显示他的核型为46，XY，r(8)(p23q24.3)[27]/45,XY,-8[3]。一个从头7.9Mb末端8p23.3p23.1缺失，27.1Mb8p23.1p11.22重复，和一个4.4Mb完整的片段，它们之间有一个正常的拷贝数，以及通过aCGHSNP阵列鉴定出具有未知临床意义的154kb母体LINGO2基因缺失（9p21.2）。通过实时PCR证实了这些畸变。根据FISH分析,8p23.1-p11.22重复是倒置的。环状染色体起源于母系8号染色体。靶向大规模平行测序未发现与Birk-Barel综合征相关的KCNK9突变。我们的数据允许假设，由于某些体细胞中环形染色体的丢失而引起的印迹基因的非活性等位基因的常染色体一元性可能是马赛克印迹障碍的病因机制。推测与较不严重的表型。
