{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T13:30:38Z","timestamp":1769693438874,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Kinase D\u2010interacting substrate of 220\u2009kDa (<jats:italic>KIDINS220<\/jats:italic>) is a transmembrane protein playing integral role in growth mediating pathways in the nervous and cardiovascular systems. <jats:italic>KIDINS220<\/jats:italic> heterozygous truncating variants that affect the protein's C\u2010terminus have been associated with a phenotype, so far described only in few unrelated children, including spastic paraplegia, intellectual disability, nystagmus, and obesity. More recently, a homozygous, more N\u2010terminal truncating variant in <jats:italic>KIDINS220<\/jats:italic> gene was suggested to be associated with enlarged cerebral ventricles and limb contractures in three fetuses from a consanguineous family. We confirm the latter finding by presenting the first detailed prenatal identification of a fetal phenotype associated with novel homozygous deleterious frameshift variant in <jats:italic>KIDINS220<\/jats:italic> gene in a consanguineous healthy Egyptian couple. History of unexplained seven miscarriages and a similar stillbirth were recorded. Prenatal ultrasonography revealed limb contractions and ventriculomegaly; in addition to previously unreported cerebellar anomalies, cardiac anomalies and hydrops fetalis. These findings represent an expansion of clinical and molecular spectrum associated with <jats:italic>KIDINS220<\/jats:italic> variants and broaden our understanding of genotype\u2013phenotype relationships in lethal congenital contractures syndromes and associated severe abnormal embryological development. More generally, our study adds <jats:italic>KIDINS220<\/jats:italic> to the rare group of genes which may cause disease by either of two distinct mutational mechanisms.<\/jats:p>","DOI":"10.1002\/ajmg.a.61858","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T16:00:51Z","timestamp":1600963251000},"page":"2867-2876","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Prenatal delineation of a distinct lethal fetal syndrome caused by a homozygous truncating <scp><i>KIDINS220<\/i><\/scp> variant"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7572-9128","authenticated-orcid":false,"given":"Sara H.","family":"El\u2010Dessouky","sequence":"first","affiliation":[{"name":"Prenatal Diagnosis and Fetal Medicine Department, Human Genetics and Genome Research Division, National Research Centre  Cairo 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