{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T03:30:48Z","timestamp":1792985448334,"version":"4.5.0"},"reference-count":20,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"WIMM Strategic Alliance","award":["G0902418"],"award-info":[{"award-number":["G0902418"]}]},{"name":"WIMM Strategic Alliance","award":["MC UU 12025"],"award-info":[{"award-number":["MC UU 12025"]}]},{"DOI":"10.13039\/100018379","name":"VTCT Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018379","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Genomics England Limited"},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["Oxford Biomedical Research Centre Program"],"award-info":[{"award-number":["Oxford Biomedical Research Centre Program"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Doctoral Training Program","award":["Medical Research Council (MRC)"],"award-info":[{"award-number":["Medical Research Council (MRC)"]}]},{"name":"Doctoral Training Program","award":["Radcliffe Department of Medicine"],"award-info":[{"award-number":["Radcliffe Department of Medicine"]}]},{"name":"Doctoral Training Program","award":["Usher Cunningham Scholarship (Exeter College, Oxfo"],"award-info":[{"award-number":["Usher Cunningham Scholarship (Exeter College, Oxfo"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T031670\/1"],"award-info":[{"award-number":["MR\/T031670\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2022,11,11]]},"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>\n                     <jats:italic>SPRY1<\/jats:italic> 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Analysis of whole-genome sequencing data from individuals with craniosynostosis enrolled in the 100,000 Genomes Project identified a likely pathogenic variant within <jats:italic>SPRY1<\/jats:italic>. Reverse-transcriptase PCR and western blot analysis were used to investigate the effect of the variant on <jats:italic>SPRY1<\/jats:italic> mRNA and protein, in lymphoblastoid cell lines from the patient and both parents.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A nonsense variant in <jats:italic>SPRY1,<\/jats:italic> encoding p.(Leu27*), was confirmed to be heterozygous in the unaffected parents and homozygous in the child. The child\u2019s 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 <jats:italic>Spry1<jats:sup>\u2212\/\u2212<\/jats:sup>\n                     <\/jats:italic> 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2022-108946","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T13:20:49Z","timestamp":1671628849000},"page":"712-716","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Craniosynostosis, inner ear, and renal anomalies in a child with complete loss of <i>SPRY1<\/i> (sprouty homolog 1) function"],"prefix":"10.1136","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1396-3765","authenticated-orcid":false,"given":"Rebecca S","family":"Tooze","sequence":"first","affiliation":[{"name":"Clinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6399-6528","authenticated-orcid":false,"given":"Eduardo","family":"Calpena","sequence":"additional","affiliation":[{"name":"Clinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5024-049X","authenticated-orcid":false,"given":"Stephen R F","family":"Twigg","sequence":"additional","affiliation":[{"name":"Clinical Genetics Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, 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