Yang Aram, Kim Jinsup, Ki Chang-Seok, Hong Sung Hwa, Cho Sung Yoon, Jin Dong-Kyu
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
BMC Med Genet. 2017 Oct 26;18(1):121. doi: 10.1186/s12881-017-0484-6.
Hypoparathyroidism, sensorineural hearing loss, and renal disease (HDR) syndrome, also known as Barakat syndrome, is a rare genetic disorder with high phenotypic heterogeneity caused by haploinsufficiency of the GATA3 gene on chromosome 10p14-p15. For these reasons, the diagnosis of HDR syndrome is challenging and requires a high index of suspicion as well as genetic analysis.
A 14-month-old boy, with sensorineural hearing loss in both ears, showed typical radiological features of X-linked stapes gusher on preoperative temporal bone computed tomography (CT) for cochlear implantations. Then after his discharge from hospital, he suffered a hypocalcemic seizure and we discovered a renal cyst during investigation of hypocalcemia. He was finally diagnosed with HDR syndrome by clinical findings, which were confirmed by molecular genetic testing. Direct sequencing of the GATA3 gene showed a heterozygous 2-bp deletion (c.1201_1202delAT), which is predicted to cause a frameshift of the reading frame (p.Met401Valfs*106).
To our knowledge, this is the first case of HDR syndrome with a novel de novo variant mimicking a congenital X-linked stapes gusher syndrome. Novel mutations and the diversity of clinical manifestations expand the genotypic and phenotypic spectrum of HDR syndrome. Diagnosis of HDR syndrome is still challenging, but clinicians should consider it in their differential diagnosis for children with a wide range of clinical manifestations including hypocalcemia induced seizures and deafness. We hope that this case will contribute to further understanding and studies of HDR-associated GATA3 mutations.
甲状旁腺功能减退、感音神经性听力损失和肾脏疾病（HDR）综合征，也称为巴拉卡特综合征，是一种罕见的遗传性疾病，具有高度的表型异质性，由10号染色体p14 - p15上GATA3基因的单倍剂量不足引起。由于这些原因，HDR综合征的诊断具有挑战性，需要高度的怀疑指数以及基因分析。
一名14个月大的男孩双耳有感音神经性听力损失，在术前颞骨计算机断层扫描（CT）检查人工耳蜗植入时显示出典型的X连锁镫骨涌综合征的放射学特征。出院后，他发生了低钙血症惊厥，在低钙血症调查期间我们发现了一个肾囊肿。最终根据临床表现诊断为HDR综合征，并通过分子遗传学检测得到证实。GATA3基因的直接测序显示杂合的2个碱基缺失（c.1201_1202delAT），预计会导致阅读框移码（p.Met401Valfs*106）。
据我们所知，这是首例具有模仿先天性X连锁镫骨涌综合征的新型新发变异的HDR综合征病例。新的突变和临床表现的多样性扩展了HDR综合征的基因型和表型谱。HDR综合征的诊断仍然具有挑战性，但临床医生在对包括低钙血症惊厥和耳聋等广泛临床表现的儿童进行鉴别诊断时应考虑到该疾病。我们希望这个病例将有助于进一步了解和研究与HDR相关的GATA3突变。
