{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:00:51Z","timestamp":1786132851529,"version":"build-2736575974"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","funder":[{"DOI":"10.13039\/501100002767","name":"The Science and Technology Innovation Program of Hunan Province","doi-asserted-by":"publisher","award":["2019SK1010"],"award-info":[{"award-number":["2019SK1010"]}],"id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002767","name":"The Science and Technology Innovation Program of Hunan Province","doi-asserted-by":"publisher","award":["2020SK2072"],"award-info":[{"award-number":["2020SK2072"]}],"id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>\n                      Bilateral renal agenesis (BRA) is a lethal form of congenital anomaly of the kidney and urinary tract, usually resulting in perinatal death or justifying termination of pregnancy. The exact causes of this disease are not clear, although genetic factors are considered important. In this study, we describe a pathological homozygous frameshift variant (\n                      <jats:italic toggle=\"yes\">NPNT<\/jats:italic>\n                      :NM_001184690:exon8:c.777dup\/p.Lys260*) that is responsible for a recessive form of BRA within a family. A knock-in mouse model mimicking the mutation we found in the family was established and replicated the phenotype of BRA. These results reveal a new genetic cause of BRA and identify a new target for genetic diagnosis, prenatal diagnosis, and preimplantation diagnosis for families with BRA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Bilateral renal agenesis (BRA) is a lethal con genital anomaly caused by the failure of normal development of both kidneys early in embryonic development. Oligohydramnios on fetal ultrasonography reveals BRA. Although the exact causes are not clear, BRA is associated with mutations in many renal development genes. However, molecular diagnostics do not pick up many clinical patients. Nephronectin (NPNT) may be a candidate protein for widening diagnosis. It is essential in kidney development, and knockout of\n                      <jats:italic toggle=\"yes\">Npnt<\/jats:italic>\n                      in mice frequently leads to kidney agenesis or hypoplasia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A consanguineous Han family experienced three cases of induced abortion in the second trimester of pregnancy, due to suspected BRA. Whole-exome sequencing (WES)\u2013based homozygosity mapping detected underlying genetic factors, and a knock-in mouse model confirmed the renal agenesis phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WES and evaluation of homozygous regions in II:3 and II:4 revealed a pathologic homozygous frameshift variant in\n                      <jats:italic toggle=\"yes\">NPNT<\/jats:italic>\n                      (NM_001184690:exon8:c.777dup\/p.Lys260*), which leads to a premature stop in the next codon. The truncated NPNT protein exhibited decreased expression, as confirmed\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      by the overexpression of WT and mutated NPNT. A knock-in mouse model homozygous for the detected\n                      <jats:italic toggle=\"yes\">Npnt<\/jats:italic>\n                      mutation replicated the BRA phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      A biallelic loss-of-function\n                      <jats:italic toggle=\"yes\">NPNT<\/jats:italic>\n                      mutation causing an autosomal recessive form of BRA in humans was confirmed by the corresponding phenotype of knock-in mice. Our results identify a novel genetic cause of BRA, revealing a new target for genetic diagnosis, prenatal diagnosis, and preimplantation diagnosis for families with BRA.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2020121762","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T14:51:05Z","timestamp":1622213465000},"page":"1871-1879","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":16,"title":["A Biallelic Frameshift Mutation in Nephronectin Causes Bilateral Renal Agenesis in Humans"],"prefix":"10.1681","volume":"32","author":[{"given":"Lei","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Xiangya Hospital Central South University, Changsha, China"},{"name":"Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Xiangya Hospital Central South University, Changsha, China"},{"name":"Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingkun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Xiangya Hospital Central South University, Changsha, China"},{"name":"Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingrui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Xiangya Hospital Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuifang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Xiangya Hospital Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Xiangya Hospital Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenlin","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Xiangya Hospital Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Xiangya Hospital Central South University, Changsha, 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