{"entity": "researcher", "timestamp": "2026-08-08T16:38:23.874Z", "family": "Puschmann", "given": "Andreas", "initials": "A", "orcid": "0000-0002-3201-8198", "affiliations": ["Department of Clinical Sciences Lund, Neurology (A.I., E.K., A.G.L., A.P.), Lund University; Section of Neurology (A.I., E.K., A.G.L., A.P.), Sk\u00e5ne University Hospital, Lund; Department of Clinical Genetics and Pathology (E.E., S.S.), Laboratory Medicine, Region Sk\u00e5ne; Department of Clinical Sciences Lund (E.E.), Division of Pathology, Lund University; Bioinformatics Core Facility (K.T.), Sahlgrenska Academy at University of Gothenburg, Sweden; Neurology (N.M.-M., J.P.), University of Helsinki, and Helsinki University Hospital, Finland; Department of Imaging and Function (C.H.), Sk\u00e5nes University Hospital, Lund; and Department of Clinical Sciences, Diagnostic Radiology (C.H.), Lund University, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/c8144cd82c4944c28c45ecdfb822fa20.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/c8144cd82c4944c28c45ecdfb822fa20"}}, "publications": [{"entity": "publication", "iuid": "fa7683a6a0ce40a48cda36eb39c141b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fa7683a6a0ce40a48cda36eb39c141b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fa7683a6a0ce40a48cda36eb39c141b3"}}, "title": "Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4: A poly-glycine disease.", "authors": [{"family": "Wallenius", "given": "Joel", "initials": "J"}, {"family": "Kafantari", "given": "Efthymia", "initials": "E"}, {"family": "Jhaveri", "given": "Emma", "initials": "E"}, {"family": "Gorcenco", "given": "Sorina", "initials": "S"}, {"family": "Ameur", "given": "Adam", "initials": "A"}, {"family": "Karremo", "given": "Christin", "initials": "C"}, {"family": "Dobloug", "given": "Sigurd", "initials": "S"}, {"family": "Karrman", "given": "Kristina", "initials": "K"}, {"family": "de Koning", "given": "Tom", "initials": "T"}, {"family": "Ilinca", "given": "Andreea", "initials": "A"}, {"family": "Landqvist Wald\u00f6", "given": "Maria", "initials": "M"}, {"family": "Arvidsson", "given": "Andreas", "initials": "A"}, {"family": "Persson", "given": "Staffan", "initials": "S"}, {"family": "Englund", "given": "Elisabet", "initials": "E"}, {"family": "Ehrencrona", "given": "Hans", "initials": "H"}, {"family": "Puschmann", "given": "Andreas", "initials": "A", "orcid": "0000-0002-3201-8198", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8144cd82c4944c28c45ecdfb822fa20.json"}}], "type": "journal article", "published": "2024-01-04", "journal": {"title": "Am. J. Hum. Genet.", "issn": "1537-6605", "volume": "111", "issue": "1", "pages": "82-95", "issn-l": "0002-9297"}, "abstract": "Autosomal-dominant ataxia with sensory and autonomic neuropathy is a highly specific combined phenotype that we described in two Swedish kindreds in 2014; its genetic cause had remained unknown. Here, we report the discovery of exonic GGC trinucleotide repeat expansions, encoding poly-glycine, in zinc finger homeobox 3 (ZFHX3) in these families. The expansions were identified in whole-genome datasets within genomic segments that all affected family members shared. Non-expanded alleles carried one or more interruptions within the repeat. We also found ZFHX3 repeat expansions in three additional families, all from the region of Sk\u00e5ne in southern Sweden. Individuals with expanded repeats developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades. Anticipation was observed in all families and correlated with different repeat lengths determined through long-read sequencing in two family members. The most severely affected individuals had marked autonomic dysfunction, with severe orthostatism as the most disabling clinical feature. Neuropathology revealed p62-positive intracytoplasmic and intranuclear inclusions in neurons of the central and enteric nervous system, as well as alpha-synuclein positivity. ZFHX3 is located within the 16q22 locus, to which spinocerebellar ataxia type 4 (SCA4) repeatedly had been mapped; the clinical phenotype in our families corresponded well with the unique phenotype described in SCA4, and the original SCA4 kindred originated from Sweden. ZFHX3 has known functions in neuronal development and differentiation n both the central and peripheral nervous system. Our findings demonstrate that SCA4 is caused by repeat expansions in ZFHX3.", "doi": "10.1016/j.ajhg.2023.11.008", "pmid": "38035881", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Long read": "Collaborative", "National Genomics Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10806739"}, {"db": "pii", "key": "S0002-9297(23)00403-2"}], "notes": [], "created": "2023-11-30T10:31:15.712Z", "modified": "2025-02-28T14:11:20.301Z"}, {"entity": "publication", "iuid": "f1f0e7c64a61473b9211064a88f06083", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f1f0e7c64a61473b9211064a88f06083.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f1f0e7c64a61473b9211064a88f06083"}}, "title": "MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor.", "authors": [{"family": "Ilinca", "given": "Andreea", "initials": "A", "orcid": "0000-0003-1979-5459", "researcher": {"href": "https://publications.scilifelab.se/researcher/83a5e949884d41e285e50cf909854cc0.json"}}, {"family": "Englund", "given": "Elisabet", "initials": "E", "orcid": "0000-0002-2708-2443", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c98fa2b2e7e4e318cd00eb1e8e3ac7a.json"}}, {"family": "Samuelsson", "given": "Sofie", "initials": "S"}, {"family": "Truv\u00e9", "given": "Katarina", "initials": "K"}, {"family": "Kafantari", "given": "Efthymia", "initials": "E"}, {"family": "Martinez-Majander", "given": "Nicolas", "initials": "N", "orcid": "0000-0001-8489-7051", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0daac2247ef4808bfba10c4622eaf7d.json"}}, {"family": "Putaala", "given": "Jukka", "initials": "J", "orcid": "0000-0002-6630-6104", "researcher": {"href": "https://publications.scilifelab.se/researcher/d068f81a5c074d1f94b2585add3956c4.json"}}, {"family": "H\u00e5kansson", "given": "Claes", "initials": "C"}, {"family": "Lindgren", "given": "Arne G", "initials": "AG", "orcid": "0000-0003-1942-7330", "researcher": {"href": "https://publications.scilifelab.se/researcher/94b604b14f1f4776a19010f5ac2a575c.json"}}, {"family": "Puschmann", "given": "Andreas", "initials": "A", "orcid": "0000-0002-3201-8198", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8144cd82c4944c28c45ecdfb822fa20.json"}}], "type": "journal article", "published": "2021-02-00", "journal": {"title": "Neurol Genet", "issn": "2376-7839", "volume": "7", "issue": "1", "pages": "e548", "issn-l": "2376-7839"}, "abstract": "To describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke.\n\nWe studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole-genome sequencing (WGS) and intrafamilial cosegregation analyses.\n\nFifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family. MAP3K6 has known functions in angiogenesis and affects vascular endothelial growth factor expression, which may be implicated in cerebrovascular disease.\n\nOur data strongly suggest the MAP3K6 variant to be causative for this novel disease phenotype, but the absence of functional data and the present lack of additional families with this disease and MAP3K6 mutations still limit the formal evidence for the variant's pathogenicity.", "doi": "10.1212/NXG.0000000000000548", "pmid": "33728376", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "NG2020014639"}, {"db": "pmc", "key": "PMC7958314"}], "notes": [], "created": "2022-11-15T12:53:29.992Z", "modified": "2022-11-15T12:53:30.167Z"}]}