Craniosynostosis, inner ear, and renal anomalies in a child with complete loss of SPRY1 (sprouty homolog 1) function.
Craniosynostosis, inner ear, and renal anomalies in a child with complete loss of SPRY1 (sprouty homolog 1) function.
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DOI：
10.1136/jmg-2022-108946
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发表时间：
2023-07
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
SPRY 1编码蛋白发芽同源物1（Spry-1），其是受体酪氨酸激酶信号传导的负调节剂。Spry-1基因突变小鼠表现出肾脏/泌尿道异常和头骨大小改变;尚未报道Spry-1在人类中完全丧失功能。对入选100，000基因组计划的颅缝早闭患者的全基因组测序数据进行分析，在SPRY 1中发现了一种可能的致病性变体。逆转录酶PCR和蛋白质印迹分析用于研究变体对患者和父母的淋巴母细胞系中SPRY 1 mRNA和蛋白的影响。SPRY 1的无义变体，编码p.（Leu 27 *），被证实在未受影响的父母中是杂合的，而在孩子中是纯合的。该儿童的表型包括矢状面颅缝早闭症、覆盖于颅缝的皮下囊性病变、与双侧耳蜗和前庭发育不良相关的听力损失以及单侧肾囊肿，与Spry 1 −/− null小鼠报告的特征重叠。功能研究支持逃避无义介导的衰变，但蛋白质印迹分析表明，在受影响的孩子和父母双方的全长蛋白质的完全缺乏显着减少。这是第一份关于人类Spry-1功能完全丧失的报告，与颅缝、内耳和肾脏的异常有关。
SPRY1 encodes protein sprouty homolog 1 (Spry-1), a negative regulator of receptor tyrosine kinase signalling. Null mutant mice display kidney/urinary tract abnormalities and altered size of the skull; complete loss-of-function of Spry-1 in humans has not been reported. Analysis of whole-genome sequencing data from individuals with craniosynostosis enrolled in the 100,000 Genomes Project identified a likely pathogenic variant within SPRY1. Reverse-transcriptase PCR and western blot analysis were used to investigate the effect of the variant on SPRY1 mRNA and protein, in lymphoblastoid cell lines from the patient and both parents. A nonsense variant in SPRY1, encoding p.(Leu27*), was confirmed to be heterozygous in the unaffected parents and homozygous in the child. The child’s phenotype, which included sagittal craniosynostosis, subcutaneous cystic lesions overlying the lambdoid sutures, hearing loss associated with bilateral cochlear and vestibular dysplasia and a unilateral renal cyst, overlapped the features reported in Spry1−/− null mice. Functional studies supported escape from nonsense-mediated decay, but western blot analysis demonstrated complete absence of full-length protein in the affected child and a marked reduction in both parents. This is the first report of complete loss of Spry-1 function in humans, associated with abnormalities of the cranial sutures, inner ear, and kidneys.
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影响因子：
30.8
作者：
Lindeboom, Rik G. H.;Vermeulen, Michiel;Supek, Fran
通讯作者：
Supek, Fran
影响因子：
--
作者：
Wright KD;Mahoney Rogers AA;Zhang J;Shim K
通讯作者：
Shim K
DOI：
10.1038/s41436-021-01297-5
发表时间：
2021-12
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Hyder Z;Calpena E;Pei Y;Tooze RS;Brittain H;Twigg SRF;Cilliers D;Morton JEV;McCann E;Weber A;Wilson LC;Douglas AGL;McGowan R;Need A;Bond A;Tavares ALT;Thomas ERA;Genomics England Research Consortium;Hill SL;Deans ZC;Boardman-Pretty F;Caulfield M;Scott RH;Wilkie AOM
通讯作者：
Wilkie AOM
DOI：
10.1523/jneurosci.0307-10.2010
发表时间：
2010-03-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Faedo A;Borello U;Rubenstein JL
通讯作者：
Rubenstein JL
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G