22q and two: 22q11.2 deletion syndrome and coexisting conditions.
22q and two: 22q11.2 deletion syndrome and coexisting conditions.
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DOI：
10.1002/ajmg.a.40494
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
McDonald-McGinn DM
中科院分区：
文献类型：
--
作者：
Cohen JL;Crowley TB;McGinn DE;McDougall C;Unolt M;Lambert MP;Emanuel BS;Zackai EH;McDonald-McGinn DM
22q11.2缺失综合征（DS）是最常见的拷贝数变异（CNV），影响约1/1，000的胎儿和约1/2，000 - 4，000的儿童，导致多器官系统中可识别但可变的结果。具有非典型特征的患者应立即考虑由于其他全基因组突变、CNV或另一等位基因突变/CNV而导致的共存诊断，从而揭示常染色体隐性疾病。重要的是，双重诊断使症状复杂化，并影响管理。我们以前报告了7例22q11.2DS患者，包括：SCID、8三体嵌合体、Bernard-Soulier和CEDNIK综合征。在这里，我们提出了6个额外的未报告的患者与22q11.2DS和并发症的诊断。回顾了1,422例22q11.2DS患者的记录，这些患者通过FISH、微阵列或MLPA鉴定，随后在费城儿童医院（CHOP）的22 q和You中心进行了随访，以确定双重诊断。除了我们先前报告的7例病例外，我们还发现了另外6例22q11.2DS和另一种共存疾病，这些疾病通过分子/细胞遗传学研究、新生儿筛查、凝血因子研究或酶检测确定;其中包括CHARGE综合症（CHD 7突变）、囊性纤维化、母系遗传的17 q12缺失、G6 PD缺陷、血管性血友病和1q21.1缺失，导致我们中心的双重诊断发生率为0.9%。在我们的队列中确定的双重诊断的范围是值得注意的，医学上可操作的，并可能改变长期结果和复发风险咨询。因此，我们的研究结果可能支持使用微阵列，其他等位基因/WES突变分析的组合来检测22q11.2DS患者，以确保适当的个性化护理，因为制定医疗管理决策取决于建立正确的诊断。
22q11.2 deletion syndrome (DS) is the most frequent copy number variant (CNV) affecting ~1/1,000 fetuses and ~1/2,000–4,000 children, resulting in recognizable but variable findings across multiple organ systems. Patients with atypical features should prompt consideration of coexisting diagnoses due to additional genome-wide mutations, CNVs, or mutations/CNVs on the other allele, unmasking autosomal recessive conditions. Importantly, a dual diagnosis compounds symptoms and impacts management. We previously reported seven patients with 22q11.2DS and: SCID, Trisomy 8 mosaicism, Bernard-Soulier, and CEDNIK syndromes. Here we present six additional unreported patients with 22q11.2DS and concurrent diagnoses. Records on 1,422 patients with 22q11.2DS, identified via FISH, microarray, or MLPA, followed in our 22q and You Center at the Children’s Hospital of Philadelphia (CHOP) were reviewed to identify a dual diagnosis. In addition to our seven previously reported cases, we identified an additional six with 22q11.2DS and another coexisting condition identified via: molecular/cytogenetic studies, newborn screening, coagulation factor studies, or enzyme testing; these include CHARGE syndrome (CHD7 mutation), cystic fibrosis, a maternally inherited 17q12 deletion, G6PD deficiency, von Willebrand disease, and 1q21.1 deletion, resulting in an incidence of dual diagnoses at our center of 0.9%. The range of dual diagnoses identified in our cohort is notable, medically actionable, and may alter long-term outcome and recurrence risk counseling. Thus, our findings may support testing patients with 22q11.2DS using a combination of microarray, mutational analysis of the other allele/WES, to ensure appropriate personalized care, as formulating medical management decisions hinges on establishing the correct diagnoses in their entirety.
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影响因子：
4
作者：
GOLDMUNTZ, E;DRISCOLL, D;EMANUEL, BS
通讯作者：
EMANUEL, BS
影响因子：
3.4
作者：
Hamilton, Scott;Husein, Murad;Dworschak-Stokan, Anne
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影响因子：
5.1
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Eicher, PS;McDonald-McGinn, DM;Zackai, EH
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作者：
Costain, Gregory;Chow, Eva W. C.;Bassett, Anne S.
通讯作者：
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影响因子：
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作者：
Goodship, J;Cross, I;Wren, C
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Wren, C