title: A novel mutation in DNAJB6, p.(Phe91Leu), in childhood-onset LGMD1D with a severe phenotype.
abstract: To identify and characterize genetic mutation in a Korean family with limb-girdle muscular dystrophy 1 (LGMD1), we analyzed in the affected family members clinical features, DNAJB6 by Sanger sequencing, muscle structures by magnetic resonance imaging (MRI), and functional consequences of the identified mutation using a zebrafish model. The clinical phenotypes along with identification of a novel c.271T > C (p.(Phe91Leu)) mutation in DNAJB6 led to the diagnosis of LGMD1D in the affected family members. This mutation presents unique clinical and radiological features compared with other DNAJB6 mutants. All affected members examined showed reduced pulmonary function, and had nasal voice and dysphagia except the two members who were thirteen and twelve years of age at the time of examination. Muscle phenotypes developed between 8 and 11 years of age and were more severe as compared to previously reported LGMD1D patients with mutant DNAJB6. Patients' MRI scans exhibited early involvement of the lateral head of gastrocnemius, in contrast to its late involvement in reported LGMD1D cases. Functional study using zebrafish embryos demonstrated that p.Phe91Leu elicits more severe muscle defects than the reported p.Phe93Leu and p.Pro96Arg mutations. We conclude that a novel p.(Phe91Leu) mutation in DNAJB6 is associated with severe childhood-onset LGMD1D.
authors.affiliation: Department of Neurology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Tai-Seung
authors.initials: TS
authors.lastname: Nam
authors.affiliation: Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Wenting
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Radiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Suk-Hee
authors.initials: SH
authors.lastname: Heo
authors.affiliation: Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Anna
authors.initials: A
authors.lastname: Cho
authors.affiliation: Department of Neurology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Pediatrics, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Young Ok
authors.initials: YO
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Chae
authors.affiliation: Department of Neurology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
authors.forename: Dae-Seong
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Neurology, Chonnam National University Medical School, Gwangju, Republic of Korea. Electronic address: mkkim@jnu.ac.kr.
authors.forename: Myeong-Kyu
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea. Electronic address: zebrafish@chonnam.ac.kr.
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000328:Adult; D017668:Age of Onset; D000818:Animals; D030801:Animals, Genetically Modified; D044466:Asian People; D002648:Child; D003937:Diagnosis, Differential; D005190:Family; D005260:Female; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D012720:Severity of Illness Index; D015027:Zebrafish
chemical_list: C485565:DNAJB6 protein, human; D050956:HSP40 Heat-Shock Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins
keywords: DNAJB6; Human genetics; Limb-girdle muscular dystrophy; Magnetic resonance imaging; Zebrafish