Familial Cerebellar Ataxia and Amyotrophic Lateral Sclerosis/Frontotemporal Dementia with DAB1 and C9ORF72 Repeat Expansions: An 18-Year Study
Standard
Familial Cerebellar Ataxia and Amyotrophic Lateral Sclerosis/Frontotemporal Dementia with DAB1 and C9ORF72 Repeat Expansions: An 18-Year Study. / Rosenbohm, Angela; Pott, Hendrik; Thomsen, Mirja; Rafehi, Haloom; Kaya, Sabine; Szymczak, Silke; Volk, Alexander E; Mueller, Kathrin; Silveira, Isabel; Weishaupt, Jochen H; Tönnies, Holger; Seibler, Philip; Zschiedrich, Katja; Schaake, Susen; Westenberger, Ana; Zühlke, Christine; Depienne, Christel; Trinh, Joanne; Ludolph, Albert C; Klein, Christine; Bahlo, Melanie; Lohmann, Katja.
In: MOVEMENT DISORD, Vol. 37, No. 12, 12.2022, p. 2427-2439.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Familial Cerebellar Ataxia and Amyotrophic Lateral Sclerosis/Frontotemporal Dementia with DAB1 and C9ORF72 Repeat Expansions: An 18-Year Study
AU - Rosenbohm, Angela
AU - Pott, Hendrik
AU - Thomsen, Mirja
AU - Rafehi, Haloom
AU - Kaya, Sabine
AU - Szymczak, Silke
AU - Volk, Alexander E
AU - Mueller, Kathrin
AU - Silveira, Isabel
AU - Weishaupt, Jochen H
AU - Tönnies, Holger
AU - Seibler, Philip
AU - Zschiedrich, Katja
AU - Schaake, Susen
AU - Westenberger, Ana
AU - Zühlke, Christine
AU - Depienne, Christel
AU - Trinh, Joanne
AU - Ludolph, Albert C
AU - Klein, Christine
AU - Bahlo, Melanie
AU - Lohmann, Katja
N1 - © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PY - 2022/12
Y1 - 2022/12
N2 - BACKGROUND: Coding and noncoding repeat expansions are an important cause of neurodegenerative diseases.OBJECTIVE: This study determined the clinical and genetic features of a large German family that has been followed for almost 2 decades with an autosomal dominantly inherited spinocerebellar ataxia (SCA) and independent co-occurrence of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).METHODS: We carried out clinical examinations and telephone interviews, reviewed medical records, and performed magnetic resonance imaging and positron emission tomography scans of all available family members. Comprehensive genetic investigations included linkage analysis, short-read genome sequencing, long-read sequencing, repeat-primed polymerase chain reaction, and Southern blotting.RESULTS: The family comprises 118 members across seven generations, 30 of whom were definitely and five possibly affected. In this family, two different pathogenic mutations were found, a heterozygous repeat expansion in C9ORF72 in four patients with ALS/FTD and a heterozygous repeat expansion in DAB1 in at least nine patients with SCA, leading to a diagnosis of DAB1-related ataxia (ATX-DAB1; SCA37). One patient was affected by ALS and SCA and carried both repeat expansions. The repeat in DAB1 had the same configuration but was larger than those previously described ([ATTTT]≈75 [ATTTC]≈40-100 [ATTTT]≈415 ). Clinical features in patients with SCA included spinocerebellar symptoms, sometimes accompanied by additional ophthalmoplegia, vertical nystagmus, tremor, sensory deficits, and dystonia. After several decades, some of these patients suffered from cognitive decline and one from additional nonprogressive lower motor neuron affection.CONCLUSION: We demonstrate genetic and clinical findings during an 18-year period in a unique family carrying two different pathogenic repeat expansions, providing novel insights into their genotypic and phenotypic spectrums. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
AB - BACKGROUND: Coding and noncoding repeat expansions are an important cause of neurodegenerative diseases.OBJECTIVE: This study determined the clinical and genetic features of a large German family that has been followed for almost 2 decades with an autosomal dominantly inherited spinocerebellar ataxia (SCA) and independent co-occurrence of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).METHODS: We carried out clinical examinations and telephone interviews, reviewed medical records, and performed magnetic resonance imaging and positron emission tomography scans of all available family members. Comprehensive genetic investigations included linkage analysis, short-read genome sequencing, long-read sequencing, repeat-primed polymerase chain reaction, and Southern blotting.RESULTS: The family comprises 118 members across seven generations, 30 of whom were definitely and five possibly affected. In this family, two different pathogenic mutations were found, a heterozygous repeat expansion in C9ORF72 in four patients with ALS/FTD and a heterozygous repeat expansion in DAB1 in at least nine patients with SCA, leading to a diagnosis of DAB1-related ataxia (ATX-DAB1; SCA37). One patient was affected by ALS and SCA and carried both repeat expansions. The repeat in DAB1 had the same configuration but was larger than those previously described ([ATTTT]≈75 [ATTTC]≈40-100 [ATTTT]≈415 ). Clinical features in patients with SCA included spinocerebellar symptoms, sometimes accompanied by additional ophthalmoplegia, vertical nystagmus, tremor, sensory deficits, and dystonia. After several decades, some of these patients suffered from cognitive decline and one from additional nonprogressive lower motor neuron affection.CONCLUSION: We demonstrate genetic and clinical findings during an 18-year period in a unique family carrying two different pathogenic repeat expansions, providing novel insights into their genotypic and phenotypic spectrums. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
U2 - 10.1002/mds.29221
DO - 10.1002/mds.29221
M3 - SCORING: Journal article
C2 - 36148898
VL - 37
SP - 2427
EP - 2439
JO - MOVEMENT DISORD
JF - MOVEMENT DISORD
SN - 0885-3185
IS - 12
ER -