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Abstract：
The terminal 14q32 duplication has been reported often in association with other cytogenetic abnormalities, and individuals with this specific duplication showed varying degrees of developmental delay/intellectual disability (DD/ID) and growth retardation (GR), and distinct facial dysmorphisms. Herein, based on the limited cases of terminal duplication of 14q32 known to date, we present new affected siblings presenting with DD/ID, GR, and facial dysmorphism, as well as cerebral infarction caused by recurrent de novo der(14)t(14;14)(p11.2;q32.1) leading to terminal duplication of 14q32. We used coverage analysis generated via duo exome sequencing, performed chromosomal microarray (CMA) as a confirmatory test, and compared our findings with those reported previously. Coverage analysis generated via duo exome sequencing revealed a 17.2 Mb heterozygous duplication at chromosome 14q32.11-q32.33 with a Z ratio ranging between 0.5 and 1 in the proband and her elder brother. As a complementary method, CMA established a terminal duplication described as the arr[hg19]14q32.11q32.33(90,043,558_107,258,824)x3 in the proband and her elder brother; however, the parents and other siblings showed normal karyotyping and no abnormal gain or loss of CMA results. Five candidate genes, BCL11B, CCNK, YY1, DYNC1H1, and PACS2, were associated with the clinical phenotypes in our cases. Although the parents had normal chromosomes, two affected cases carrying terminal duplication of 14q32 can be explained by gonadal mosaicism. Further studies are needed to establish the association between cerebrovascular events and terminal duplication of chromosome 14q32, including investigation into the cytogenetics of patients with precise clinical descriptions.
摘要：
据报道，末端14q32重复常与其他细胞遗传学异常相关，具有这种特定重复的个体表现出不同程度的发育迟缓/智力残疾（DD/ID）和生长迟缓（GR），和明显的面部畸形。在这里，根据迄今为止已知的14q32终端重复的有限案例，我们展示了新的受影响的兄弟姐妹出现DD/ID，GR,和面部畸形，以及由复发引起的脑梗死（14）t（14;14）（p11.2;q32.1）导致14q32的末端重复。我们使用了通过二重外显子组测序产生的覆盖率分析，进行染色体微阵列（CMA）作为确认测试，并将我们的发现与之前报道的结果进行了比较。通过二重外显子组测序产生的覆盖分析显示，在染色体14q32.11-q32.33处存在17.2Mb的杂合重复，先证者和她的哥哥的Z比率在0.5到1之间。作为一种补充方法，CMA在先证者和她的哥哥中建立了一个终端重复，称为ARR[hg19]14q32.11q32.33（90,043,558_107,258,824）x3；但是，父母和其他兄弟姐妹的核型分析正常,CMA结果无异常增减.五个候选基因,BCL11B,CCNK,YY1，DYNC1H1和PACS2与我们病例的临床表型有关。虽然父母的染色体正常,2例携带末端重复14q32的受影响病例可通过性腺镶嵌性来解释。需要进一步的研究来建立脑血管事件与染色体14q32末端重复之间的关联，包括对具有精确临床描述的患者的细胞遗传学进行调查。
