Identification of a rare 17p13.3 duplication including the BHLHA9 and YWHAE genes in a family with developmental delay and behavioural problems
Identification of a rare 17p13.3 duplication including the BHLHA9 and YWHAE genes in a family with developmental delay and behavioural problems
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DOI：
10.1186/1471-2350-13-93
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发表时间：
2012-10-04
影响因子：
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通讯作者：
Gimelli, Giorgio
中科院分区：
文献类型：
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作者：
Capra, Valeria;Mirabelli-Badenier, Marisol;Gimelli, Giorgio
背景：PAFAH1B1和YWHAE基因在17p13.3的缺失和重复与不同的临床表型有关。特别是，PAFAH1B1的缺失会导致孤立的无脑畸形，而PAFAH1B1和YWHAE的缺失会导致Miller-Dieker综合征。PAFAH1B1的单独重复与轻度发育迟缓和低眼压有关，而YWHAE的单独重复与自闭症有关。特别是，与PAFAH1B1或YWHAE重复相关的不同畸形特征表明，有必要根据参与染色体复制的基因将患者的临床特征分为两组。方法：采用经典细胞遗传学和阵列CGH分析方法对先证者及其家族进行分析。结果：我们通过FISH和ARRAY-CGH分离了一个17p13.3重复序列，该重复序列长达329.5个碱基，涉及YWHAE基因，而不是PAFAH1B1，受轻度畸形表型的影响，并伴有自闭症和智力低下。我们认为BHLHA9、YWHAE和CRK基因与我们的患者的表型有关。结论：我们报道了另一例仅含有BHLHA9、YWHAE和CRK基因的17p13.3小重复染色体家族性病例。我们的观察和其他类似微重复的病例有望得到诊断，并将有助于更好地描述与17p13.3微重复相关的临床表型谱。
Background: Deletions and duplications of the PAFAH1B1 and YWHAE genes in 17p13.3 are associated with different clinical phenotypes. In particular, deletion of PAFAH1B1 causes isolated lissencephaly while deletions involving both PAFAH1B1 and YWHAE cause Miller-Dieker syndrome. Isolated duplications of PAFAH1B1 have been associated with mild developmental delay and hypotonia, while isolated duplications of YWHAE have been associated with autism. In particular, different dysmorphic features associated with PAFAH1B1 or YWHAE duplication have suggested the need to classify the patient clinical features in two groups according to which gene is involved in the chromosomal duplication.Methods: We analyze the proband and his family by classical cytogenetic and array-CGH analyses. The putative rearrangement was confirmed by fluorescence in situ hybridization.Results: We have identified a family segregating a 17p13.3 duplication extending 329.5 kilobases by FISH and array-CGH involving the YWHAE gene, but not PAFAH1B1, affected by a mild dysmorphic phenotype with associated autism and mental retardation. We propose that BHLHA9, YWHAE, and CRK genes contribute to the phenotype of our patient. The small chromosomal duplication was inherited from his mother who was affected by a bipolar and borderline disorder and was alcohol addicted.Conclusions: We report an additional familial case of small 17p13.3 chromosomal duplication including only BHLHA9, YWHAE, and CRK genes. Our observation and further cases with similar microduplications are expected to be diagnosed, and will help better characterise the clinical spectrum of phenotypes associated with 17p13.3 microduplications.