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It is a serious condition that requires extensive medical care as it indicates severe fetal compromise. We clinically evaluated four patients from two branches of a highly consanguineous family from the UAE with NIHF using whole exome sequencing and <jats:italic>in silico<\/jats:italic> analysis. Fetal onset pleural and peritoneal effusions were detected in all four patients and were born with moderate to severe hydrops fetalis that resolved with age. Follow up showed relatively normal growth and development apart from mild ascites and haemangiomas in all affected children, recurrent hydrocele in all affected males, intestinal malabsorption in two patients, dysmorphic features in two patients, and congenital cardiac defects in three out of four patients. Molecular testing identified a homozygous eight nucleotide deletion in <jats:italic>THSD1<\/jats:italic> gene (NM_199263:c.1163_1170delGGCCAGCC, p.Arg388Glnfs*66) as the underlying cause of this phenotype in the affected children. The novel variant cosegregates with the described phenotype in an autosomal recessive mode of inheritance and is predicted to be pathogenic as it leads to a truncated protein that lost important structural and functional domains. Thrombospondin\u20101 domain containing protein 1 gene <jats:italic>THSD1<\/jats:italic> has been recently associated with of NIHF and embryonic lethality. Here, we report the novel truncating <jats:italic>THSD1<\/jats:italic> variant, and describe new clinical features that have not been reported previously thus expanding the phenotype associate with loss\u2010of\u2010function mutations in <jats:italic>THSD1<\/jats:italic> causing NIHF.<\/jats:p>","DOI":"10.1002\/ajmg.a.40424","type":"journal-article","created":{"date-parts":[[2018,7,29]],"date-time":"2018-07-29T07:28:19Z","timestamp":1532849299000},"page":"1996-2003","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A recessive truncating variant in thrombospondin\u20101 domain containing protein 1 gene <i>THSD1<\/i> is the underlying cause of nonimmune hydrops fetalis, congenital cardiac defects, and haemangiomas in four patients from a consanguineous family"],"prefix":"10.1002","volume":"176","author":[{"given":"Hanadi A.","family":"Abdelrahman","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine and Heath Sciences United Arab Emirates University Al\u2010Ain  United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisha","family":"Al\u2010Shamsi","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Tawam Hospital  Al\u2010Ain United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"John","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine and Heath Sciences United Arab Emirates University Al\u2010Ain  United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozef","family":"Hertecant","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Tawam Hospital  Al\u2010Ain United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Lootah","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Tawam Hospital  Al\u2010Ain United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassam R.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine and Heath Sciences United Arab Emirates University Al\u2010Ain  United Arab Emirates"},{"name":"Zayed Center for Health Sciences United Arab Emirates University  Al\u2010Ain United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-2218","authenticated-orcid":false,"given":"Lihadh","family":"Al\u2010Gazali","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine and Heath Sciences United Arab Emirates University Al\u2010Ain  United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36988"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34438"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32655"},{"issue":"11","key":"e_1_2_8_5_1","first-page":"4317","article-title":"Genetic marking of hematopoietic stem and endothelial cells: Identification of the Tmtsp gene encoding a novel cell surface protein with the thrombospondin\u20101 domain","volume":"107","author":"Dc W.","year":"2012","journal-title":"Blood"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki412"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw015"},{"issue":"6","key":"e_1_2_8_8_1","first-page":"996","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent W. 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