Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0003635 (
apraxia
)
2,817
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
An in depth study of
PSEN1
mutation p.Thr116Ile (c.335C>T) is presented from two Korean families with autosomal dominant inheritance. Clinical manifestation of our patients included memory loss, attention deficits, visuospatial dysfunction, agnosia, aphasia,
apraxia
, and personality changes, which occurred in their 30s.
PSEN1
Thr116Ile was initially discovered in an Italian patient and two French families with early onset Alzheimer's disease (EOAD) with similar age of onset. To verify the possible pathogenic mechanisms of mutation,
in silico
predictions and 3D modeling were performed. Structure predictions revealed significant aberrations in first hydrophilic loop (HL-I loop). The hydrophobic isoleucine could alter the loop orientation through increased hydrophobic contacts with the surrounding amino acids. Mutation could destroy a possible hydrogen bond between tyrosine 115 and
threonine
116, which may affect the loop conformation. HL-I was confirmed as a conservative region of
PSEN1
, which may be critical in
PSEN1
functions. An additional pathogenic mutation,
PSEN1
Thr116Asn, was also found for the same residue, where the patient presented young onset AD (YOND). Other mutations in HL-I loop, such as Tyr115His and Glu120Asp, were described in patients with YOND, supporting the critical role of HL-I loop in
PSEN1
activity.
...
PMID:
PSEN1
p.Thr116Ile Variant in Two Korean Families with Young Onset Alzheimer's Disease. 3020 May 36
