TY - JOUR
T1 - A Novel Homozygous p.R1105X Mutation of the AP4E1 Gene in Twins with Hereditary Spastic Paraplegia and Mycobacterial Disease
AU - Kong, Xiao Fei
AU - Bousfiha, Aziz
AU - Rouissi, Abdelfettah
AU - Itan, Yuval
AU - Abhyankar, Avinash
AU - Bryant, Vanessa
AU - Okada, Satoshi
AU - Ailal, Fatima
AU - Bustamante, Jacinta
AU - Casanova, Jean Laurent
AU - Hirst, Jennifer
AU - Boisson-Dupuis, Stéphanie
N1 - Funding Information:
YI is supported by the AXA Research Fund. JLC has a research grant from the Jeffrey Modell Foundation in collaboration with Talecris BioTherapeutics. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
PY - 2013/3/5
Y1 - 2013/3/5
N2 - We report identical twins with intellectual disability, progressive spastic paraplegia and short stature, born to a consanguineous family. Intriguingly, both children presented with lymphadenitis caused by the live Bacillus Calmette-Guérin (BCG) vaccine. Two syndromes - hereditary spastic paraplegia (HSP) and mycobacterial disease - thus occurred simultaneously. Whole-exome sequencing (WES) revealed a homozygous nonsense mutation (p.R1105X) of the AP4E1 gene, which was confirmed by Sanger sequencing. The p.R1105X mutation has no effect on AP4E1 mRNA levels, but results in lower levels of AP-4ε protein and of the other components of the AP-4 complex, as shown by western blotting, immunoprecipitation and immunofluorescence. Thus, the C-terminal part of the AP-4ε subunit plays an important role in maintaining the integrity of the AP-4 complex. No abnormalities of the IL-12/IFN-γ axis or oxidative burst pathways were identified. In conclusion, we identified twins with autosomal recessive AP-4 deficiency associated with HSP and mycobacterial disease, suggesting that AP-4 may play important role in the neurological and immunological systems.
AB - We report identical twins with intellectual disability, progressive spastic paraplegia and short stature, born to a consanguineous family. Intriguingly, both children presented with lymphadenitis caused by the live Bacillus Calmette-Guérin (BCG) vaccine. Two syndromes - hereditary spastic paraplegia (HSP) and mycobacterial disease - thus occurred simultaneously. Whole-exome sequencing (WES) revealed a homozygous nonsense mutation (p.R1105X) of the AP4E1 gene, which was confirmed by Sanger sequencing. The p.R1105X mutation has no effect on AP4E1 mRNA levels, but results in lower levels of AP-4ε protein and of the other components of the AP-4 complex, as shown by western blotting, immunoprecipitation and immunofluorescence. Thus, the C-terminal part of the AP-4ε subunit plays an important role in maintaining the integrity of the AP-4 complex. No abnormalities of the IL-12/IFN-γ axis or oxidative burst pathways were identified. In conclusion, we identified twins with autosomal recessive AP-4 deficiency associated with HSP and mycobacterial disease, suggesting that AP-4 may play important role in the neurological and immunological systems.
UR - http://www.scopus.com/inward/record.url?scp=84874629660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874629660&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0058286
DO - 10.1371/journal.pone.0058286
M3 - Article
C2 - 23472171
AN - SCOPUS:84874629660
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 3
M1 - e58286
ER -