PMID- 29971521
OWN - NLM
STAT- MEDLINE
DCOM- 20190926
LR  - 20190926
IS  - 1364-6753 (Electronic)
IS  - 1364-6745 (Linking)
VI  - 19
IP  - 3
DP  - 2018 Aug
TI  - R106C TFG variant causes infantile neuroaxonal dystrophy "plus" syndrome.
PG  - 179-187
LID - 10.1007/s10048-018-0552-x [doi]
AB  - TFG (tropomyosin-receptor kinase fused gene) encodes an essential protein in the 
      regulation of vesicular trafficking between endoplasmic reticulum and Golgi 
      apparatus. The homozygous variant c.316C > T within TFG has been previously 
      associated with a complicated hereditary spastic paraplegia (HSP) phenotype in 
      two unrelated Indian families. Here, we describe the first Italian family with 
      two affected siblings harboring the same variant, who in childhood were 
      classified as infantile neuroaxonal dystrophy (INAD) based on clinical and 
      neuropathological findings. Twenty years after the first diagnosis, exome 
      sequencing was instrumental to identify the genetic cause of this disorder and 
      clinical follow-up of patients allowed us to reconstruct the natural history of 
      this clinical entity. Investigations on patient's fibroblasts demonstrate the 
      presence of altered mitochondrial network and inner membrane potential, 
      associated with metabolic impairment. Our study highlights phenotypic 
      heterogeneity characterizing individuals carrying the same pathogenic variant in 
      TFG and provides an insight on tight connection linking mitochondrial efficiency 
      and neuronal health to vesicular trafficking.
FAU - Catania, A
AU  - Catania A
AD  - Molecular Neurogenetics Unit, IRCCS Foundation, C. Besta Neurological Institute, 
      Via L. Temolo n. 4, 20126, Milan, Italy.
AD  - Department of Medicine and Surgery, PhD Programme in Molecular and Translational 
      Medicine, Milan Bicocca University, Via Cadore 48, 20900, Monza, Italy.
FAU - Battini, R
AU  - Battini R
AD  - IRCCS Fondazione Stella Maris, Calambrone, Pisa, Italy.
AD  - Department of Experimental Medicine, University of Pisa, Pisa, Italy.
FAU - Pippucci, T
AU  - Pippucci T
AD  - Medical Genetics Unit, San'Orsola-Malpighi University Hospital, Via Giuseppe 
      Massarenti 9, 40138, Bologna, Italy.
FAU - Pasquariello, R
AU  - Pasquariello R
AD  - IRCCS Fondazione Stella Maris, Calambrone, Pisa, Italy.
FAU - Chiapparini, M L
AU  - Chiapparini ML
AD  - Neuroradiology, Foundation IRCCS, Neurological Institute "C. Besta", Milan, 
      Italy.
FAU - Seri, M
AU  - Seri M
AD  - Medical Genetics Unit, Sant'Orsola-Malpighi University Hospital, Department of 
      Medical and Surgical Sciences, University of Bologna, Via Giuseppe Massarenti 9, 
      40138, Bologna, Italy.
FAU - Garavaglia, B
AU  - Garavaglia B
AD  - Molecular Neurogenetics Unit, IRCCS Foundation, C. Besta Neurological Institute, 
      Via L. Temolo n. 4, 20126, Milan, Italy.
FAU - Zorzi, G
AU  - Zorzi G
AD  - Child Neurology Unit, Foundation IRCCS, Neurological Institute C. Besta, Milan, 
      Italy.
FAU - Nardocci, N
AU  - Nardocci N
AD  - Child Neurology Unit, Foundation IRCCS, Neurological Institute C. Besta, Milan, 
      Italy.
FAU - Ghezzi, D
AU  - Ghezzi D
AD  - Molecular Neurogenetics Unit, IRCCS Foundation, C. Besta Neurological Institute, 
      Via L. Temolo n. 4, 20126, Milan, Italy.
AD  - Department of Pathophysiology and Transplantation, University of Milan, Milan, 
      Italy.
FAU - Tiranti, V
AU  - Tiranti V
AUID- ORCID: 0000-0002-3584-7338
AD  - Molecular Neurogenetics Unit, IRCCS Foundation, C. Besta Neurological Institute, 
      Via L. Temolo n. 4, 20126, Milan, Italy. valeria.tiranti@istituto-besta.it.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180703
PL  - United States
TA  - Neurogenetics
JT  - Neurogenetics
JID - 9709714
RN  - 0 (Proteins)
RN  - 0 (TFG protein, human)
RN  - 94ZLA3W45F (Arginine)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Adult
MH  - Amino Acid Substitution/genetics
MH  - Arginine/genetics
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Child
MH  - Child, Preschool
MH  - Consanguinity
MH  - Cysteine/genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Mutation, Missense
MH  - Neuroaxonal Dystrophies/*genetics
MH  - Pedigree
MH  - Proteins/*genetics
MH  - Siblings
MH  - Spastic Paraplegia, Hereditary/genetics
OTO - NOTNLM
OT  - Axonal spheroids
OT  - Endoplasmic reticulum
OT  - INAD- TFG
OT  - Mitochondria
EDAT- 2018/07/05 06:00
MHDA- 2019/09/27 06:00
CRDT- 2018/07/05 06:00
PHST- 2018/05/24 00:00 [received]
PHST- 2018/06/15 00:00 [accepted]
PHST- 2018/07/05 06:00 [pubmed]
PHST- 2019/09/27 06:00 [medline]
PHST- 2018/07/05 06:00 [entrez]
AID - 10.1007/s10048-018-0552-x [pii]
AID - 10.1007/s10048-018-0552-x [doi]
PST - ppublish
SO  - Neurogenetics. 2018 Aug;19(3):179-187. doi: 10.1007/s10048-018-0552-x. Epub 2018 
      Jul 3.