Expanding the clinical and mutational spectrum of germline ABL1 mutations-associated syndrome: A case report
Expanding the clinical and mutational spectrum of germline ABL1 mutations-associated syndrome: A case report
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DOI：
10.1097/md.0000000000014782
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发表时间：
2019-03-01
期刊：
影响因子：
1.6
通讯作者：
Borrego, Salud
中科院分区：
文献类型：
--
作者：
Bravo-Gil, Nereida;Marcos, Irene;Borrego, Salud
基本原理：罕见综合征患者的临床和基因管理通常是一项困难、困惑和缓慢的任务。患者关注：患有多系统疾病的男性儿童患者表现为先天性心脏缺陷、面部畸形、骨骼畸形和眼睛异常。诊断：患者一直处于临床未确诊状态，直到基因结果确定，并允许将其临床特征与种系ABL1突变相关综合征联系起来。干预：我们进行了全外显子组测序，以揭示该患者潜在的遗传缺陷。结果：唯一检测到的与该病相容的变异是ABL1(c.434_436del；p.Ser145del)中一种新的杂合性非移码新缺失。受影响的残基位于蛋白质的功能结构域，在不同的物种中高度保守，其丢失被预测为致病。课程：我们的结果加强了ABL1参与临床未诊断的发育缺陷病例，并扩大了最近报道的ABL1相关综合征的临床和基因谱。在这个意义上，我们描述了第三个胚系ABL1致病突变，并首次将眼前房异常与这种病理联系起来。因此，我们认为这种疾病可能比目前认为的更具异质性，并可能与其他多系统疾病重叠，因此应该考虑对这类病例的遗传学和临床重新评估，以确保正确的诊断。
Rationale:Clinical and genetic management of patients with rare syndromes is often a difficult, confusing, and slow task.Patient concerns:Male child patient with a multisystemic disease showing congenital heart defects, facial dysmorphism, skeletal malformations, and eye anomalies.Diagnosis:The patient remained clinically undiagnosed until the genetic results were conclusive and allowed to associate its clinical features with the germline ABL1 mutations-associated syndrome.Interventions:We performed whole-exome sequencing to uncover the underlying genetic defect in this patient. Subsequently, family segregation of identified mutations was performed by Sanger sequencing in all available family members.Outcomes:The only detected variant compatible with the disease was a novel heterozygous nonframeshift de novo deletion in ABL1 (c.434_436del; p.Ser145del). The affected residue lays in a functional domain of the protein, it is highly conserved among distinct species, and its loss is predicted as pathogenic by in silico studies.Lessons:Our results reinforce the involvement of ABL1 in clinically undiagnosed cases with developmental defects and expand the clinical and genetic spectrum of the recently reported ABL1-associated syndrome. In this sense, we described the third germline ABL1 causative mutation and linked, for the first time, ocular anterior chamber anomalies to this pathology. Thus, we suggest that this disorder may be more heterogeneous than is currently believed and may be overlapping with other multisystemic diseases, hence genetic and clinical reassessment of this type of cases should be considered to ensure proper diagnosis.