Clinical characterization of int22h1/int22h2-mediated Xq28 duplication/deletion: new cases and literature review.
Clinical characterization of int22h1/int22h2-mediated Xq28 duplication/deletion: new cases and literature review.
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DOI：
10.1186/s12881-015-0157-2
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发表时间：
2015-03-14
影响因子：
--
通讯作者：
Cheung SW
中科院分区：
文献类型：
--
作者：
El-Hattab AW;Schaaf CP;Fang P;Roeder E;Kimonis VE;Church JA;Patel A;Cheung SW
Int 22 h1/int 22 h2介导的Xq 28重复综合征是由内含子22同源区1（int 22 h1）和2（int 22 h2）之间的非等位基因同源重组介导的~0.5 Mb染色体重复引起的，除了int 22 h3外，这也是破坏血友病A中F8基因倒位的原因。这种综合征最近被描述在9名男性与认知障碍，行为问题，和独特的面部特征;和6名女性与轻度表型。先前在母亲和女儿中报告了相互缺失。这表明，这种缺失可能没有表现型的影响，在女性，因为偏斜的X染色体失活，但可能是胚胎致死的男性。使用基于寡核苷酸的染色体微阵列进行阵列比较基因组杂交分析。在AR（雄激素受体）和FMR 1（脆性X智力低下1）位点进行了X染色体失活研究。我们在这里提出了5名男性和6名女性int 22 h1/int 22 h2介导的Xq 28重复综合征。男性表现出认知障碍、行为问题和独特的面部特征。6只雌性动物中有2只表现出轻度认知障碍。这种重复是母系遗传的，在大多数携带重复的女性中观察到偏斜的X染色体失活。我们还报告了一个母亲和女儿的相互删除超重，但正常的认知。此外，我们提出了第一例产前诊断的从头int 22 h1/int 22 h2介导的缺失在一个健康的女婴。我们回顾了以前报道的具有相似或重叠重排的个体，并评估了重排区域基因的潜在作用。int 22 h1/int 22 h2介导的Xq 28重复个体之间的临床特征的相似性支持了这种重复导致可识别的综合征的概念，该综合征影响男性，女性表现出较温和的表型。提示该综合征中观察到的认知障碍是由于位于重复区域内的RAB 39 B基因剂量增加所致。CLIC 2的剂量增加也可能有助于表型。相互缺失导致X染色体失活，女性无临床表型。重叠缺失的审查表明，VBP 1的半合子丢失可能是与该缺失相关的拟定雄性致死性的原因。
Int22h1/int22h2-mediated Xq28 duplication syndrome is caused by ~0.5 Mb chromosomal duplications mediated by nonallelic homologous recombination between intron 22 homologous region 1 (int22h1) and 2 (int22h2), which, in addition to int22h3, are also responsible for inversions disrupting the F8 gene in hemophilia A. This syndrome has recently been described in 9 males with cognitive impairment, behavioral problems, and distinctive facial features; and 6 females with milder phenotypes. The reciprocal deletion was previously reported in a mother and daughter. It was suggested that this deletion may not have phenotypic effects in females because of skewed chromosome X inactivation, but may be embryonic lethal in males. Array comparative genomic hybridization analyses were performed using oligonucleotide-based chromosomal microarray. Chromosome X inactivation studies were performed at the AR (androgen receptor) and FMR1 (fragile X mental retardation 1) loci. We present here 5 males and 6 females with int22h1/int22h2-mediated Xq28 duplication syndrome. The males manifested cognitive impairment, behavioral problems, and distinctive facial features. Two of the six females manifested mild cognitive impairment. This duplication was maternally inherited, and skewed chromosome X inactivation was observed in the majority of females carrying the duplication. We also report the reciprocal deletion in a mother and daughter with overweight, but normal cognition. In addition, we present the first case of a prenatally diagnosed de novo int22h1/int22h2-mediated deletion in a healthy female infant. We reviewed individuals previously reported with similar or overlapping rearrangements and evaluated the potential roles of genes in the rearrangement region. The similarity of clinical features among individuals with the int22h1/int22h2-mediated Xq28 duplication supports the notion that this duplication causes a recognizable syndrome that affects males with females exhibiting milder phenotypes. It is suggested that the observed cognitive impairment in this syndrome results from increased dosage of RAB39B gene located within the duplicated region. Increased dosage of CLIC2 may also contribute to the phenotype. The reciprocal deletion results in skewed chromosome X inactivation and no clinical phenotype in females. Review of overlapping deletions suggests that hemizygous loss of VBP1 may be the cause for the proposed male lethality associated with this deletion.
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影响因子：
5.3
作者：
El-Hattab AW;Smolarek TA;Walker ME;Schorry EK;Immken LL;Patel G;Abbott MA;Lanpher BC;Ou Z;Kang SH;Patel A;Scaglia F;Lupski JR;Cheung SW;Stankiewicz P
通讯作者：
Stankiewicz P
影响因子：
3.9
作者：
Vanmarsenille, Lieselot;Giannandrea, Maila;Froyen, Guy
通讯作者：
Froyen, Guy
影响因子：
3.5
作者：
Collins, AL;Levenson, JM;Zoghbi, HY
通讯作者：
Zoghbi, HY
影响因子：
5.3
作者：
Sharp, A;Robinson, D;Jacobs, P
通讯作者：
Jacobs, P
影响因子：
9.8
作者：
Giannandrea, Maila;Bianchi, Veronica;D'Adamo, Patrizia
通讯作者：
D'Adamo, Patrizia