Department of Otolaryngology-Head and Neck Surgery, Children's Hospital of Fudan University, Shanghai, China.
Center for Molecular Medicine, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, China.
Mol Genet Genomic Med. 2020 May;8(5):e1222. doi: 10.1002/mgg3.1222. Epub 2020 Mar 10.
Barakat syndrome is an autosomal dominant disorder characterized by the triad of hypoparathyroidism, sensorineural deafness, and renal anomalies and is caused by mutations in GATA3 gene. SLC34A3 is the cause gene of hypophosphatemic rickets with hypercalciuria, and heterozygous carriers may have milder clinical symptoms. The aim of this study was to identify the underlying genetic cause of a patient who initially presented with renal failure, hypercalciuria, kidney stone, and bilateral sensorineural deafness.
A 6-year-old boy with complex clinical presentations was investigated. Comprehensive medical evaluations were performed including auditory function tests, endocrine function tests, metabolic studies, and imaging examinations. Molecular diagnoses were analyzed by trio whole-exome sequencing.
One novel de novo deleterious variant (c. 324del) of the GATA3 gene was identified in the patient. The patient can be diagnosed with Barakat syndrome. In addition, one novel variant (c. 589A>G) of the SLC34A3 gene was detected, which was inherited from the father. This heterozygous variant can explain the hypercalciuria and kidney stone that occurred in both the patient and his father.
This study provides a special case which is phenotype-driven dual diagnoses, and the two novel variants can parsimoniously explain the complex clinical presentations of this patient.
Barakat 综合征是一种常染色体显性遗传疾病，其特征为三联征，包括甲状旁腺功能减退、感觉神经性耳聋和肾脏异常，由 GATA3 基因突变引起。SLC34A3 是低磷血症性佝偻病伴高钙尿症的致病基因，杂合子携带者可能具有更轻微的临床症状。本研究旨在确定一名最初表现为肾衰竭、高钙尿症、肾结石和双侧感觉神经性耳聋的患者的潜在遗传病因。
对一名具有复杂临床表现的 6 岁男孩进行了研究。进行了全面的医学评估，包括听觉功能测试、内分泌功能测试、代谢研究和影像学检查。通过 trio 全外显子组测序分析分子诊断。
在患者中发现了一个新的无义变异体（c.324del），该变异体是 GATA3 基因的新生致病变异。该患者可以被诊断为 Barakat 综合征。此外，还检测到 SLC34A3 基因的一个新变异体（c.589A>G），该变异体来自父亲。这种杂合变异体可以解释患者及其父亲发生的高钙尿症和肾结石。
本研究提供了一个特殊的表型驱动双重诊断病例，这两个新变异体可以简洁地解释该患者的复杂临床表现。
