To describe the phenotype in 2 sisters with a rare constellation of neurologic symptoms and secretory impairments and to identify the etiology by the use of whole-genome sequencing (WGS).

After an extensive workup failed to reveal the cause of disease, in a girl with a previously not reported phenotype, WGS of the proband, her diseased older sister, an older healthy brother, and their parents was performed, and potentially pathogenic variants were analyzed.

The proband and her older sister both presented with neonatal Staphylococcus aureus parotitis, apneas, disappearance of the Moro reflex, and hypotonia. The proband survived. Her brain MRI showed white matter and basal ganglia abnormalities, and CSF damage biomarkers were increased. At age 8 years, she exhibits a constellation of symptoms including severe neurodevelopmental disorder, hearing impairment, gastrointestinal problems, and a striking lack of tear fluid, saliva, and sweat. Her respiratory mucosa is dry with potentially life-threatening mucus plugging. Through WGS, 2 loss-of-function variants in SLC12A2 were identified that follow an autosomal recessive inheritance pattern.

Taken together with a single previously reported case and the close resemblance to the phenotypes of corresponding mouse models, our study firmly establishes biallelic variants in SLC12A2 as causing human disease and adds data regarding the neurologic phenotype.

描述具有罕见神经症状和分泌障碍的 2 个姐妹的表型，并通过使用全基因组测序 (WGS) 确定病因。

在广泛的检查未能揭示疾病的原因后，对一名先前未报告表型的女孩进行了 WGS 的先证者、她患病的姐姐、一个健康的哥哥和他们的父母，并分析了潜在的致病变异。

先证者和她的姐姐都出现了新生儿金黄色葡萄球菌腮腺炎、呼吸暂停、莫罗反射消失和肌张力减退。先证者幸免于难。她的脑部 MRI 显示白质和基底节异常，脑脊液损伤生物标志物增加。在 8 岁时，她表现出一系列症状，包括严重的神经发育障碍、听力障碍、胃肠道问题，以及明显缺乏泪液、唾液和汗水。她的呼吸道黏膜干燥，黏液堵塞可能危及生命。通过 WGS，鉴定了SLC12A2中的 2 个功能丧失变体，它们遵循常染色体隐性遗传模式。

结合先前报道的单个病例以及与相应小鼠模型表型的密切相似性，我们的研究确定了SLC12A2中的双等位基因变体导致人类疾病，并添加了有关神经表型的数据。