{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T06:51:07Z","timestamp":1782543067598,"version":"3.54.5"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,7,28]],"date-time":"2018-07-28T00:00:00Z","timestamp":1532736000000},"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":[[2018,8]]},"abstract":"<jats:p>Hypoparathyroidism\u2010retardation\u2010dysmorphism syndrome (HRD) is a rare autosomal recessive disorder attributed to the mutations in the tubulin\u2010specific chaperone E (<jats:italic>TBCE<\/jats:italic>) gene, which is vital for microtubule function during mitosis, organelle positioning, and neuronal cytokinesis. HRD is a congenital syndromic hypoparathyroidism associated with growth deficiency, microcephaly, intellectual disability, ocular anomalies, and facial dysmorphism. To our knowledge, there is only one published case of mild HRD\u2010like syndrome with no identifiable genetic etiology. We report a case of severe<jats:italic>TBCE<\/jats:italic>\u2010negative phenotypic HRD in a 4\u2010year\u2010old female from India presenting with hypocalcemic seizures due to congenital hypoparathyroidism, extreme microcephaly, growth deficiency, ocular anomalies, and facial dysmorphism. SNP microarray and whole exome sequencing (WES) did not detect any abnormalities in<jats:italic>TBCE<\/jats:italic>or other genes of interest. WES revealed two variants of unknown clinical significance in<jats:italic>CASC5<\/jats:italic>gene, which codes for a protein in the kinetochore and, interestingly similar to<jats:italic>TBCE<\/jats:italic>, is essential for proper microtubule function during mitosis and cell proliferation and has been implicated in primary microcephaly disorders. However, further targeted sequencing in the parents revealed both variants inherited from the unaffected mother. Significant copy number variant noise in the proband and her parents limited further analysis. At this time the role of variants in the<jats:italic>CASC5<\/jats:italic>gene is unclear and cannot explain our patient's phenotype. In conclusion, we report a severe case of phenotypic HRD syndrome, in which extensive genetic evaluation failed to reveal an etiology. Our case demonstrates that the pathogenesis of HRD may be genetically heterogenous, meriting further genetic investigations.<\/jats:p>","DOI":"10.1002\/ajmg.a.38851","type":"journal-article","created":{"date-parts":[[2018,7,29]],"date-time":"2018-07-29T07:26:16Z","timestamp":1532849176000},"page":"1768-1772","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A case of severe<i>TBCE<\/i>\u2010negative hypoparathyroidism\u2010retardation\u2010dysmorphism syndrome: Case report and literature review"],"prefix":"10.1002","volume":"176","author":[{"given":"Anna","family":"Ryabets\u2010Lienhard","sequence":"first","affiliation":[{"name":"Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles University of Southern California Keck School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1934-1270","authenticated-orcid":false,"given":"Satja","family":"Issaranggoon na Ayuthaya","sequence":"additional","affiliation":[{"name":"Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles University of Southern California Keck School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Graham","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics Cedars\u2010Sinai Medical Center and Harbor\u2010UCLA Medical Center, David Geffen School of Medicine at UCLA Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pisit","family":"Pitukcheewanont","sequence":"additional","affiliation":[{"name":"Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles University of Southern California Keck School of Medicine Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2012.01.004"},{"issue":"5","key":"e_1_2_9_3_1","first-page":"527","article-title":"Sanjad Sakati syndrome: A case series from Jordan","volume":"18","author":"Albaramki J.","year":"2012","journal-title":"Eastern Mediterranean Health Journal\u2009=\u2009La Revue De Sante De La Mediterranee Orientale\u2009=\u2009Al\u2010Majallah Al\u2010Sihhiyah Li\u2010Sharq Al\u2010Mutawassit"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.483"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31122"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990702)85:1<48::AID-AJMG9>3.0.CO;2-Y"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds386"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/TACG.S82105"},{"issue":"3","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"e401","DOI":"10.18295\/2075-0528.1607","article-title":"New Ocular Associations in Sanjad\u2010Sakati Syndrome: Case report from Oman","volume":"14","author":"Haider A. 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