锌是一种必需的微量元素。人类食物中缺乏锌会导致生长迟缓、皮肤损伤、性腺功能低下和频繁感染。缺乏Slc30a7的小鼠会患上轻度的锌缺乏，并且容易发生前列腺癌和胰岛素抵抗。以往并未报告过人类SLC30A7（ZNT7）基因中引起疾病的突变或变异。在这里，我们介绍了来自法国家庭的两个男孩兄弟，他们生长迟缓、睾丸发育不良和骨髓衰竭。外显子测序揭示了他们从各自未受影响的父母那里继承的ZNT7中的复合杂合突变，包括NM_133496.5:c.21dup; p.Asp8ArgfsTer3和c.842+15 T>C。c.21dup变异导致ZNT7编码序列第1外显子生成一个过早的终止密码。RNA-seq分析表明，c.842+15 T>C突变导致一个漏斗式的mRNA剪接事件，在第8外显子的剪接供体位点之后生成过早的终止密码子。此外，与对照细胞相比，受影响的兄弟的ZNT7蛋白表达显著降低了80-96％。这些发现强烈暗示，应该将双等位体在SLC30A7中的变异视为生长迟缓、睾丸发育不良和综合性骨髓衰竭的原因。由牛津大学出版社2023年发表。

Zinc is an essential trace mineral. Dietary zinc deficiency results in stunted growth, skin lesions, hypogonadism, and frequent infections in humans. Mice genetically lacking Slc30a7 suffer from mild zinc deficiency and are prone to development of prostate cancer and insulin resistance. Disease-causing variants or mutations in the human SLC30A7 (ZNT7) gene have not been previously reported. Here we describe two-boy siblings from a French family with stunted growth, testicular hypoplasia, and bone marrow failure. Exome sequencing revealed compound heterozygous variants in ZNT7 consisting of NM_133496.5:c.21dup; p.Asp8ArgfsTer3 and c.842 + 15 T > C inherited from their unaffected mother and father, respectively. The c.21dup variant led to a premature stop codon generated in exon 1 of the ZNT7 coding sequence. RNA-seq analysis demonstrated that the c.842 + 15 T > C variant resulted in a leaky mRNA splicing event generating a premature stop codon right after the splicing donor site of exon 8. Moreover, the expression of ZNT7 protein was remarkably reduced by 80-96% in the affected brothers compared to the control cells. These findings strongly suggest that biallelic variants in SLC30A7 should be considered as a cause of growth retardation, testicular hypoplasia, and syndromic bone marrow failure.Published by Oxford University Press 2023.