Barakat综合征是一种常染色体显性疾病,其特征是甲状旁腺功能减退三联症,感觉神经性耳聋,和肾脏异常,是由GATA3基因突变引起的。SLC34A3是高钙尿症低磷酸盐血症的病因基因,和杂合携带者可能有较轻的临床症状。这项研究的目的是确定最初出现肾衰竭的患者的潜在遗传原因,高钙尿症,肾结石,和双侧感音神经性耳聋。
研究了一个临床表现复杂的6岁男孩。进行了全面的医学评估,包括听觉功能测试,内分泌功能试验,代谢研究,和影像学检查。通过三全外显子组测序分析分子诊断。
一个新颖的从头有害变体(c。在患者中鉴定出GATA3基因的324del)。患者可被诊断为Barakat综合征。此外,一种新颖的变体(c。589A>G)的SLC34A3基因被检测到,是从父亲那里继承的。这种杂合变体可以解释患者及其父亲发生的高钙尿症和肾结石。
这项研究提供了一种特殊情况,即表型驱动的双重诊断,这两个新的变种可以巧妙地解释该患者的复杂临床表现。
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.