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We describe two siblings and a first cousin who had severe oligohydramnios in the second trimester, and presented at birth with loose skin, wide fontanelles and sutures, and pulmonary insufficiency. Two had refractory hypotension during their brief lives and one received palliative care after birth. All were found to have a homozygous nonsense variant, <jats:italic>REN<\/jats:italic>: c.891delG; p.Tyr287*, on exome sequencing. Autopsy limited to the genitourinary system in two of the children revealed normal renal tubular histology in both. Immunoblotting confirmed diminished expression of renin within cultured skin fibroblasts. To our knowledge, this is the first identification of an association between biallelic variants in <jats:italic>REN<\/jats:italic> and oligohydramnios in the absence of renal tubular dysgenesis. Due to its role in the RAAS, it has previously been proposed that the decreased expression of REN results in hypotension, ischemia, and decreased urine production. We suggest sequencing of genes in the RAAS, including <jats:italic>REN<\/jats:italic>, should be considered in cases of severe early onset oligohydramnios, even when renal morphology and histology are normal.<\/jats:p>","DOI":"10.1002\/ajmg.a.61780","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T03:14:25Z","timestamp":1598584465000},"page":"2284-2290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A novel homozygous variant in <scp><i>REN<\/i><\/scp> in a family presenting with classic features of disorders involving the renin\u2013angiotensin pathway, without renal tubular dysgenesis"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-9304","authenticated-orcid":false,"given":"Allison A.","family":"Dilliott","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Schulich School of Medicine and Dentistry Western 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