caa a22 4500 44536436X CHVBK 20180317142925.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s10048-010-0260-7 doi (NATIONALLICENCE)springer-10.1007/s10048-010-0260-7 Partial SPAST and DPY30 deletions in a Japanese spastic paraplegia type 4 family [Elektronische Daten] [Shiroh Miura, Hiroki Shibata, Hiroshi Kida, Kazuhito Noda, Takayuki Toyama, Naoka Iwasaki, Akiko Iwaki, Mitsuyoshi Ayabe, Hisamichi Aizawa, Takayuki Taniwaki, Yasuyuki Fukumaki] Spastic paraplegia type 4 (SPG4) is the most common autosomal dominant hereditary SPG caused by mutations in the SPAST gene. We studied the four-generation pedigree of a Japanese family with autosomal dominant hereditary SPG both clinically and genetically. Twelve available family members (ten affected; two unaffected) and two spouses were enrolled in the study. The clinical features were hyperreflexia in all four limbs, spasticity of the lower extremities, impaired vibration sense, mild cognitive impairment confirmed by the Wechsler Adult Intelligence Scale—Third Edition, and peripheral neuropathy confirmed by neurophysiological examinations. All four female patients experienced miscarriages. The cerebrospinal fluid tau levels were mildly increased in two of three patients examined. Linkage analyses revealed the highest logarithm of odds score of 2.64 at 2p23-p21 where the SPAST gene is located. Mutation scanning of the entire exonic regions of the SPAST gene by direct sequencing revealed no mutations. Exonic copy number analysis by real-time quantitative polymerase chain reaction revealed heterozygous deletion of exons 1 to 4 of the SPAST gene. Breakpoint analysis showed that the centromeric breakpoint was located within intron 4 of SPAST while the telomeric breakpoint was located within intron 3 of the neighboring DPY30 gene, causing a deletion of approximately 70kb ranging from exons 1 to 3 of DPY30 to exons 1 to 4 of SPAST. To our knowledge, this is the first report of SPG4 associated with partial deletions of both the SPAST and DPY30 genes. The partial heterozygous deletion of DPY30 could modify the phenotypic expression of SPG4 patients with this pedigree. Springer-Verlag, 2010 Deletion nationallicence Hereditary spastic paraplegia type 4 (SPG4) nationallicence Neuropathy nationallicence Miscarriage nationallicence SPAST nationallicence DPY30 nationallicence tau nationallicence Miura Shiroh Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut Shibata Hiroki Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan aut Kida Hiroshi Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut Noda Kazuhito Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut Toyama Takayuki Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut Iwasaki Naoka Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut Iwaki Akiko Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan aut Ayabe Mitsuyoshi Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut Aizawa Hisamichi Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut Taniwaki Takayuki Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut Fukumaki Yasuyuki Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan aut neurogenetics Springer-Verlag 12/1(2011-02-01), 25-31 1364-6745 12:1<25 2011 12 10048 https://doi.org/10.1007/s10048-010-0260-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10048-010-0260-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Miura Shiroh Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut NATIONALLICENCE 700 1- Shibata Hiroki Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan aut NATIONALLICENCE 700 1- Kida Hiroshi Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut NATIONALLICENCE 700 1- Noda Kazuhito Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut NATIONALLICENCE 700 1- Toyama Takayuki Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut NATIONALLICENCE 700 1- Iwasaki Naoka Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut NATIONALLICENCE 700 1- Iwaki Akiko Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan aut NATIONALLICENCE 700 1- Ayabe Mitsuyoshi Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut NATIONALLICENCE 700 1- Aizawa Hisamichi Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut NATIONALLICENCE 700 1- Taniwaki Takayuki Division of Respirology, Neurology and Rheumatology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Fukuoka, Japan aut NATIONALLICENCE 700 1- Fukumaki Yasuyuki Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan aut NATIONALLICENCE 773 0- neurogenetics Springer-Verlag 12/1(2011-02-01), 25-31 1364-6745 12:1<25 2011 12 10048 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer