{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:18:11Z","timestamp":1791044291435,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,3,2]],"date-time":"2012-03-02T00:00:00Z","timestamp":1330646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Primary ciliary dyskinesia (PCD) is a genetic disorder, usually autosomal recessive, causing early respiratory disease and later subfertility. Whole exome sequencing may enable efficient analysis for locus heterogeneous disorders such as PCD. We whole\u2010exome\u2010sequenced one consanguineous Saudi Arabian with clinically diagnosed PCD and normal laterality, to attempt <jats:italic>ab initio<\/jats:italic> molecular diagnosis.<\/jats:p><jats:p>We reviewed 13 known PCD genes and potentially autozygous regions (extended homozygosity) for homozygous exon deletions, non\u2010dbSNP codon, splice\u2010site base variants or small indels. Homozygous non\u2010dbSNP changes were also reviewed exome\u2010wide. One single molecular read representing <jats:italic>RSPH9<\/jats:italic> p.Lys268del was observed, with no wild\u2010type reads, and a notable deficiency of mapped reads at this location. Among all observations, <jats:italic>RSPH9<\/jats:italic> was the strongest candidate for causality. Searching unmapped reads revealed seven more mutant reads. Direct assay for p.Lys268del (MboII digest) confirmed homozygosity in the affected individual, then confirmed homozygosity in three siblings with bronchiectasis. Our finding in southwest Saudi Arabia indicates that p.Lys268del, previously observed in two Bedouin families (Israel, UAE), is geographically widespread in the Arabian Peninsula. Analogous with cystic fibrosis <jats:italic>CFTR<\/jats:italic> p.Phe508del, screening for <jats:italic>RSPH9<\/jats:italic> p.Lys268del (which lacks sentinel dextrocardia) in those at risk would help in early diagnosis, tailored clinical management, genetic counselling and primary prevention.<\/jats:p>","DOI":"10.1111\/j.1469-1809.2012.00704.x","type":"journal-article","created":{"date-parts":[[2012,3,5]],"date-time":"2012-03-05T15:44:37Z","timestamp":1330962277000},"page":"211-220","source":"Crossref","is-referenced-by-count":22,"title":["From a Single Whole Exome Read to Notions of Clinical Screening: Primary Ciliary Dyskinesia and <i>RSPH9<\/i> p.Lys268del in the Arabian Peninsula"],"prefix":"10.1111","volume":"76","author":[{"given":"Muslim M.","family":"AlSaadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom R.","family":"Gaunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Boustred","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip A. I.","family":"Guthrie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Lenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucille","family":"Rainbow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid K.","family":"Alharbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian N. M.","family":"Day","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/03630260802508384"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.7.080505.115610"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.727"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e318203cff2"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.01.011"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr330"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prrv.2009.02.001"},{"key":"e_1_2_8_9_1","first-page":"347","article-title":"Primary ciliary dyskinesia: Genes, candidate genes and chromosomal regions","volume":"45","author":"Geremek M.","year":"2004","journal-title":"J Appl Genet"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E09-02-0155"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8202715"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3003.1999.13f28.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.10.018"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100223"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.03.018"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200850"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.726"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1516"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2009.00559.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1186802"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1172"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.08.002"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1086\/503875"},{"key":"e_1_2_8_28_1","volume-title":"SourceGeneReviews [Internet]","author":"Zariwala M. 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