{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:10:08Z","timestamp":1776791408456,"version":"3.51.2"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Calpainopathies constitute a heterogeneous group of disorders resulting from deficiencies in calpains, calcium\u2010specific proteases that modulate substrates by limited proteolysis. Clinical manifestations depend on tissue\u2010specific expression of the defective calpain and substrate specificity.\n                    <jats:italic>CAPN15<\/jats:italic>\n                    , encoding the Drosophila small optic lobes (sol) homolog, was recently found to cause various eye defects in individuals carrying bi\u2010allelic missense variants. Here we report on two siblings with manifestations reminiscent of Johanson\u2010Blizzard syndrome including failure to thrive, microcephaly, global developmental delay, dysmorphic features, endocrine abnormalities and congenital malformations, in addition to eye abnormalities. Exome sequencing identified a homozygous 47 base\u2010pair deletion in a minimal intron of\n                    <jats:italic>CAPN15<\/jats:italic>\n                    , including the splice donor site. Sequencing of cDNA revealed single exon skipping, resulting in an out\u2010of\u2010frame deletion with a predicted premature termination codon. These findings expand the phenotypic spectrum associated with\n                    <jats:italic>CAPN15<\/jats:italic>\n                    variants, and suggest that complete loss\u2010of\u2010function is associated with a recognizable syndrome of congenital malformations and developmental delay, overlapping Johanson\u2010Blizzard syndrome and the recently observed brain defects in\n                    <jats:italic>Capn15<\/jats:italic>\n                    knockout (KO) mice. Moreover, the data highlight the unique opportunity for indel detection in minimal introns.\n                  <\/jats:p>","DOI":"10.1111\/cge.13920","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T09:41:48Z","timestamp":1610271708000},"page":"577-582","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Biallelic deletion in a minimal\n                    <scp>\n                      <i>CAPN15<\/i>\n                    <\/scp>\n                    intron in siblings with a recognizable syndrome of congenital malformations and developmental delay"],"prefix":"10.1111","volume":"99","author":[{"given":"Hagar","family":"Mor\u2010Shaked","sequence":"first","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"},{"name":"Faculty of Medicine Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Somaya","family":"Salah","sequence":"additional","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"},{"name":"Genetic Unit Palestine Red Crescent Society Hospital  Hebron Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shira","family":"Yanovsky\u2010Dagan","sequence":"additional","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vardiella","family":"Meiner","sequence":"additional","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"},{"name":"Faculty of Medicine Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osama M.","family":"Atawneh","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Palestine Red Crescent Society Hospital  Hebron Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bassam","family":"Abu\u2010Libdeh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Makassed Hospital and Al\u2010Quds Medical School  East Jerusalem Palestine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orly","family":"Elpeleg","sequence":"additional","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"},{"name":"Faculty of Medicine Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3595-7075","authenticated-orcid":false,"given":"Tamar","family":"Harel","sequence":"additional","affiliation":[{"name":"Department of Genetics Hadassah Medical Center  Jerusalem Israel"},{"name":"Faculty of Medicine Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.212"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2011.08.005"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww133"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt661"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122352"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.05189-11"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.2.1105"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.16.7214"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/bio.2015.0032"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa198"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-104259"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti774"},{"issue":"5","key":"e_1_2_9_16_1","first-page":"114","article-title":"The 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