{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:43:28Z","timestamp":1789742608455,"version":"4.0.1"},"reference-count":13,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T00:00:00Z","timestamp":1498003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004253","name":"Quaid-i-Azam University","doi-asserted-by":"publisher","award":["2013\u201014"],"award-info":[{"award-number":["2013\u201014"]}],"id":[{"id":"10.13039\/501100004253","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005037","name":"Bo\u011fazi\u00e7i \u00dcniversitesi","doi-asserted-by":"publisher","award":["Grant 7695"],"award-info":[{"award-number":["Grant 7695"]}],"id":[{"id":"10.13039\/501100005037","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>We report on nine members of a consanguineous Pakistani family with primary presentation of intellectual disability, developmental delay, limb and gait ataxia, behavioral and speech problems, and tremor. By linkage mapping and exome sequencing we identified novel homozygous splicing variant c.6375\u20101G&gt;C in <jats:italic>SPTBN2<\/jats:italic>. To date, only two other <jats:italic>SPTBN2<\/jats:italic> mutations with recessive pattern of inheritance causing SCAR14 (spinocerebellar ataxia, autosomal recessive 14) that manifest with developmental ataxia and cognitive impairment, or cerebellar ataxia, mental retardation, and pyramidal signs have been reported. The mutation we identified is predicted to lead to the deletion of just the pleckstrin homology domain; thus, the earlier onset and more progressive nature of the disease in the presented family, as compared to earlier reports, were unexpected. No other mutation that could possibly explain the features that were unusual for SCAR14\u2014arched palate, limb hypotonia, climacophobia, and behavioral problems\u2014was identified. The disease was more severe in males than females. Our findings expand the recessive <jats:italic>SPTBN2<\/jats:italic> mutation phenotype. We also review <jats:italic>SPTBN2<\/jats:italic> mutation phenotypes. The gene encodes beta\u2010III spectrin, which forms tetramers with alpha\u2010II spectrin. The manifestations of this third recessive mutation suggest that for recessive mutations either no mutant protein is synthesized because the transcript is subject to nonsense\u2010mediated decay or the mutant protein does not bind membrane proteins and, thus, does not exert a negative effect in heterozygotes, whereas the dominant mutations causing SCA5 form defective tetramers that compete with the native tetramers in binding membrane proteins, but are unable to anchor them.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38332","type":"journal-article","created":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T10:52:49Z","timestamp":1498042369000},"page":"2494-2499","source":"Crossref","is-referenced-by-count":24,"title":["Progressive SCAR14 with unclear speech, developmental delay, tremor, and behavioral problems caused by a homozygous deletion of the SPTBN2 pleckstrin homology domain"],"prefix":"10.1002","volume":"173","author":[{"given":"Esra","family":"Y\u0131ld\u0131z B\u00f6l\u00fckba\u015f\u0131","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics Bo\u011fazi\u00e7i University Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Afzal","sequence":"additional","affiliation":[{"name":"Human Genetics Program, Faculty of Biological Sciences, Department of Animal Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Mumtaz","sequence":"additional","affiliation":[{"name":"Human Genetics Program, Faculty of Biological Sciences, Department of Animal Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nafees","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Genetic Engineering Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajid","family":"Malik","sequence":"additional","affiliation":[{"name":"Human Genetics Program, Faculty of Biological Sciences, Department of Animal Sciences Quaid\u2010i\u2010Azam University Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0328-6046","authenticated-orcid":false,"given":"Asl\u0131han","family":"Tolun","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Bo\u011fazi\u00e7i University Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-012-0408-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1331-2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.150"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1728"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/35065091"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812454331"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.02.001"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/membranes5040646"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003074"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(98)01208-0"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv117"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/15.17.7155"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2014.74"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.38332","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38332","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T20:26:58Z","timestamp":1696537618000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,21]]},"references-count":13,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1002\/ajmg.a.38332"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38332","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,21]]}}}