Van den Bossche et al. Supplemental Data

Phenotypic characteristics of Alzheimer patients carrying an ABCA7 mutation

Tobi Van den Bossche, MD,1,2,3,4 Kristel Sleegers, MD, PhD,1,2 Elise Cuyvers, MSc,1,2 Sebastiaan Engelborghs, MD, PhD,2,4 Anne Sieben, MD, PhD,1,2,5 Arne De Roeck, MSc,1,2 Caroline Van Cauwenberghe, MSc,1,2 Steven Vermeulen, MSc,1,2 Marleen Van den Broeck, BSc,1,2 Annelies Laureys, BSc,1,2 Karin Peeters, BSc,1,2 Maria Mattheijssens, BSc,1,2 Mathieu Vandenbulcke, MD, PhD,6,7 Rik Vandenberghe, MD, PhD,6,8 Jean-Jacques Martin, MD, PhD,2 Peter P De Deyn, MD, PhD,2,4, Patrick Cras, MD, PhD,2,3 Christine Van Broeckhoven, PhD, DSc1,2* on behalf of the Belgian Neurology consortium†.

1 Neurodegenerative Brain Diseases group, Department of Molecular Genetics, VIB, Antwerp, Belgium

2 Institute Born-Bunge, University of Antwerp, Antwerp, Belgium

3 Department of Neurology, Antwerp University Hospital, Edegem, Belgium

4 Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA), Middelheim and Hoge Beuken, Antwerp, Belgium

5 Department of Neurology, University Hospital Ghent and University of Ghent, Ghent, Belgium

6 Department of Neurosciences, Faculty of Medicine, KU Leuven, Leuven, Belgium

7 Department of Old Age Psychiatry and Memory Clinic, University Hospitals Leuven, Leuven, Belgium

8 Department of Neurology, University Hospitals Leuven, Leuven, Belgium

Peter P. De Deyn is also affiliated to the Department of Neurology and Alzheimer research Center, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands

† Belgium Neurology (BELNEU) consortium members: Dirk Nuytten (Hospital Network Antwerp, Antwerp, Belgium); Patrick Santens, Jan de Bleeker, Bart Dermaut (University Hospital Ghent, Ghent, Belgium); Olivier Deryck, Bruno Bergmans (AZ Sint-Jan Brugge, Bruges, Belgium); Alex Michotte, Jan Versijpt (University Hospital Brussels, Brussels, Belgium); Christiana Willems (Jessa Hospital, Hasselt, Belgium); Jean Delbeck (AZ Sint-Maria, Halle); Adrian Ivanoiu (Saint-Luc University Hospital, Brussels, Belgium); Eric Salmon (University of Liege and Memory Clinic, CHU Liege, Liege, Belgium)

*Corresponding author:
Prof. Dr. Christine Van Broeckhoven, PhD DSc

Neurodegenerative Brain Diseases group

VIB Department of Molecular Genetics

University of Antwerp – CDE

Universiteitsplein 1, B-2610, Antwerp, Belgium

Tel +32 3 265 1101, Fax +32 3 265 1112

E-mail:

Table e-1. Phenotypical characteristics of ABCA7 mutation carriers.

A. Cognitive features.

Patient ID / Mutation / DD at evaluation / MMSE / Amnesia / Disorientation time/place / Language dysfunction / Executive dysfunction / Attention / concentration / Dyscalculia / Dyspraxia
DR170.1 / p.E709fs / 6 / +1 / + / + / +
DR73 / p.E709fs / 4 / 13 / +1 / + / + / + / + / +
DR469 / p.E709fs / 3 / 1 / +1 / + / + / + / + / + / +
DR1087 / p.E709fs / 4 / +1 / + / + / +
DR1088 / p.E709fs / 8 / 3 / +1 / + / + / + / +
DR400 / p.E709fs / ≥1 / 18 / +1 / + / + / + / + / + / +
DR1090 / p.E709fs / 1 / 22 / + / +
DR1091 / p.E709fs / 6 months / 25 / +1 / + / + / + / + / +
DR1092 / p.E709fs / 1 / 18 / +1 / + / - / + / + / +
DR1093 / p.E709fs / 1 / 14 / +1
DR1094 / p.E709fs / 5 / +1
DR1228 / p.V541fs / 2 / 19 / +1 / + / + / + / + / +
DR1229 / p.W1214* / ≥1 / +1 / + / + / + / + / +
DR945 / p.Q1401fs / ≥1 / 19 / +1 / + / + / + / + / +
DR851 / p.R1564* / 2 / 13 / +1 / + / + / +
DR1230 / p.A2045fs / ≥6 months / +1 / + / +1 / - / + / + / -
DR1231 / c.67-1G>A / 3 / 17 / +1 / + / + / + / + / +
DR474 / c.67-1G>A / ≥1 / 15 / +1 / + / - / + / +

1: presenting symptom(s); DD = disease duration in years; + = feature is present; - = feature is absent; empty = feature is not described

B. Behavioral and clinical features.

Patient ID / Mutation / DD at evaluation / Agitation / Disinhibition / Apathy / Depression / Hallucinations / Delusions / FRS / EPS / Epilepsy
DR170.1 / p.E709fs / 6 / + / - / - / - / + / -
DR73 / p.E709fs / 4 / + / - / + / - / + / - / -
DR469 / p.E709fs / 3 / + / + / + / - / - / - / - / -
DR1087 / p.E709fs / 4 / + / + / - / - / -
DR1088 / p.E709fs / 8 / + / + / - / + / - / -
DR400 / p.E709fs / ≥1 / + / + / - / + / - / - / + / +
DR1090 / p.E709fs / 1 / - / + / - / + / - / - / +1 / -
DR1091 / p.E709fs / 6 months / -
DR1092 / p.E709fs / 1 / + / + / + / - / - / -
DR1093 / p.E709fs / 1 / + / + / - / - / - / - / -
DR1094 / p.E709fs / 5 / + / - / - / + / + / -
DR1228 / p.V541fs / 2 / - / -
DR1229 / p.W1214* / ≥1 / + / - / - / -
DR945 / p.Q1401fs / ≥1 / + / + / + / + / + / - / -
DR851 / p.R1564* / 2 / + / + / + / + / + / - / -
DR1230 / p.A2045fs / ≥6 months / + / - / - / -
DR1231 / c.67-1G>A / 3 / + / + / - / - / - / -
DR474 / c.67-1G>A / ≥1 / + / - / - / - / +

1: presenting symptom(s); DD = disease duration in years; EPS = extrapyramidal signs; FRS = frontal release signs (palmomental reflex, snout reflex and/or glabellar tap) at neurological examination; + = feature is present; - = feature is absent; empty = feature is not described

Figure e-1. Disease liability risk curve for ABCA7 mutation carriers.

Abbreviation: LOF = loss-of-function.

Figure e-2 – Hippocampal atrophy in ABCA7 mutation carrier on brain MRI.

A coronal T2-weighted brain MRI image in DR945 showing diffuse (sub)cortical and bilateral hippocampal atrophy.

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