{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:15:57Z","timestamp":1791468957086,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,6,12]],"date-time":"2015-06-12T00:00:00Z","timestamp":1434067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A new form of congenital muscular dystrophy (CMD) with multisystem involvement and characteristic mitochondrial structural changes, due to choline kinase beta (<jats:italic>CHKB<\/jats:italic>) gene defects has been characterized by intellectual disability, autistic features, ichthyosis\u2010like skin changes, and dilated cardiomyopathy. We define the clinical characteristics in 15 patients, from 14 unrelated families with so\u2010called \u2018megaconial CMD\u2019, all having mutations in <jats:italic>CHKB<\/jats:italic>. Core clinical phenotype included global developmental delay prominent in gross\u2010motor and language domains, severe intellectual disability (ID), and\/or muscle weakness in all cases. Muscle biopsies were equivocally \u2018megaconial\u2019 in all. Other peculiarities were: ichthyosis\u2010like skin changes (<jats:italic>n<\/jats:italic>\u2009=\u200911), increased serum CK levels (<jats:italic>n<\/jats:italic>\u2009=\u200912), microcephaly (<jats:italic>n<\/jats:italic>\u2009=\u20096), dysmorphic facial features (<jats:italic>n<\/jats:italic>\u2009=\u20097), neonatal hypotonia (<jats:italic>n<\/jats:italic>\u2009=\u20093), seizures (<jats:italic>n<\/jats:italic>\u2009=\u20093), epileptiform activity without clinically overt seizures (<jats:italic>n<\/jats:italic>\u2009=\u20092), dilated cardiomyopathy (<jats:italic>n<\/jats:italic>\u2009=\u20092), decreased left ventricular systolic function (<jats:italic>n<\/jats:italic>\u2009=\u20092), congenital heart defects (<jats:italic>n<\/jats:italic>\u2009=\u20093), sensorineural (<jats:italic>n<\/jats:italic>\u2009=\u20091), and conductive hearing loss (<jats:italic>n<\/jats:italic>\u2009=\u20091). Ten patients had cranial neuroimaging (MRI\u2010MRS) study, which was notably normal in all, other than one patient having a decreased choline: creatine peak. Intra\u2010familial variability in clinical expression of the disease is noted in four families. Two siblings from the same family, one presenting with global developmental delay and dilated cardiomyopathy, and the other with ichthyosis, ID and proximal weakness without cardiomyopathy died at the ages of 2 years 1 month, and 7 years 4 months respectively. Evolution was progressive (<jats:italic>n<\/jats:italic>\u2009=\u200913) and static (<jats:italic>n<\/jats:italic>\u2009=\u20092).<\/jats:p>","DOI":"10.1007\/s10545-015-9856-2","type":"journal-article","created":{"date-parts":[[2015,6,11]],"date-time":"2015-06-11T10:56:50Z","timestamp":1434020210000},"page":"1099-1108","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Clinical characteristics of megaconial congenital muscular dystrophy due to choline kinase beta gene defects in a series of 15 patients"],"prefix":"10.1002","volume":"38","author":[{"given":"Goknur","family":"Haliloglu","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology Hacettepe University Children's Hospital Ankara 06100 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beril","family":"Talim","sequence":"additional","affiliation":[{"name":"Pediatric Pathology Unit Hacettepe University Children's Hospital Ankara 06100 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cigdem Genc","family":"Sel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Dr. Sami Ulus Research and Training Hospital of Women's and Children's Health and Diseases Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haluk","family":"Topaloglu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Hacettepe University Children's Hospital Ankara 06100 Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.12.011"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","unstructured":"Cabrera\u2010SerranoM JunckerstorffRC AtkinsonVet al (accepted article in press)Novel CHKB mutation expands the megaconial muscular dystrophy phenotype.Muscle Nervedoi: 10.1002\/mus.24446","DOI":"10.1002\/mus.24446"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","unstructured":"Castro\u2010GagoM Dacruz\u2010AlvarezD Pintos\u2010MartinezEet al (2014)Exome sequencing identifies a CHKB mutation in Spanish patient with megaconial congenital muscular dystrophy and mtDNA depletion.Eur J Pediatr Neuroldoi: 10.1016\/j.ejpn.2014.06.005","DOI":"10.1016\/j.ejpn.2014.06.005"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.126"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","unstructured":"Garcia\u2010CazorlaAMochelFLamariFSaudubrayJMThe clinical spectrum of inherited diseases involved in the synthesis and remodeling of complex lipids. 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