arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in Argentina. Arteropatia cerebral autosomal dominante com infartos subcorticais e.
Subcortical Infarcts and Leukoencephalopathy: Structural MR Imaging Changes and. Apolipoprotein E Genotype. R. van den Boom. S.A.J. Lesnick. Oberstein.
normal: in particular there were no Dohle bodies. A bleeding time was greater than 20 minutes. Tests for anti-nuclear antibody and dsDNA antibody were.
Apr 14, 2012 - Cowden's disease, also known as a kind of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome, is an uncommon auto-.
We performed both manual and automated ... generalized autocalibrating partial parallel acquisition; MPRAGE, magnetization-prepared rapid gradient-echo; MRI, magnetic resonance .... eration factor of 2, b value = 1500 s/mm2). ...... Yushkevich, P.A.,
Jun 6, 2017 - Cardiac complications. Left ventricular hypertrophy. Valvular complications. Mitral valve prolapse. Mitral regurgitation. Aortic regurgitation.
Apr 14, 2012 - nancies including breast, thyroid and endometrial carcinoma are the hallmark of the disease. ... dominal CT scan presented hemangiomas approximately 2. Fig. ... and 2.7 cm in size in both lobes of the liver, and a gallbladder.
Howe Laboratory of Ophthalmology and the Berman-Gund Laboratory for the Study of Retinal Degenerations, ... structure of rhodopsin, 3 of the 17 mutant amino acids are ..... Foundation Fighting Blindness, the George Gund Foundation, the.
PP2. Missense variant in a gene that has a low rate of benign missense variation. Only one benign missense variant (rs2287949) was hit for a total of 1593 bp of ...
Supplementary Table. Applicable criteria for classifying variants with evidence of pathogenicity according to the ACMG Standards and Guidelines (2015) used in this study. Classification
Evidence of pathogenicity
Applicable evidence in this study
Null variant (nonsense, frameshift, splice,
NA
Very strong PVS1
initiation codon, exon(s) deletion) in a gene where LOF is a known mechanism of disease Strong PS1
Same amino acid change as a previously
NA
established pathogenic variant PS2
De novo
NA
PS3
Well-established in vitro or in vivo functional
NA
studies PS4
The prevalence of the variant in affected
NA
individuals is significantly increased Moderate PM1
Located in a mutational hot spot and/or critical
The Major Facilitator Superfamily (MFS, db_xref,
functional domain
CDD:304372) at 34-232 or MFS/sugar transport protein (db_xref, CDD: 257676) at codons 35-524, (https://www.ncbi.nlm.nih.gov/protein); Transmembrane domain at codons 70-92 (http://www.cbs.dtu.dk/services/TMHMM/); 3 mutations are reported around the transmembrane domain as G64S, G89R
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and D93N (Reinders A, Ward JM. Mol Med Rep 2015;12:1393-1398) PM2
Absent
from
controls
(or
extremely
low
frequency if recessive)
Absent in “dbSNP138*”, “1000 Genomes Project data (2015Aug)*”, “NHLBI-ESP project with 6500 exomes*”, “ExAC 65000 exome allele frequency data*”, and “DBexome**”
PM3
For recessive disorders, detected in trans with
NA
a pathogenic variant PM4
Protein length changes as a result of in-frame
NA
deletions/insertions in a nonrepeat region PM5
Novel missense change at an amino acid
NA
residue where a different missense change determined to be pathogenic has been seen before (eg. R38C, R38G) PM6
Assumed to be de novo (without confirmation)
NA
Cosegregation with disease in multiple affected
LOD score of 2.00~3.56 in the region (this study)
Supporting PP1
family members PP2
Missense variant in a gene that has a low rate
Only one benign missense variant (rs2287949) was hit for a
of benign missense variation
total of 1593 bp of the coding sequence of the SLC45A2 gene***
PP3
Multiple
lines
of
computational
evidence
support a deleterious effect on the gene
“Pathogenic/Disease causing/Damaging” for Polyphen-2 (http://genetics.bwh.harvard.edu/pph2/), SIFT (http://sift.jcvi.org), PROVEAN (http://provean.jcvi.org), MCAP
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(http://bejerano.stanford.edu/mcap/) and Mutation Taster (http://www.mutationtaster.org). PP4
Patient’s phenotype or family history is highly
NA
specific for a disease with a single genetic etiology PP5
Reputable source recently reports variant as
NA
pathogenic (no laboratory evidence) Note that the combing criteria of PM1, PM2, PP1, PP2 and PP3 falls into “Likely pathogenic” as (v): 2 Moderate (PM1-PM6) AND 2 Supporting (PP1-PP5) according to ACMG Standards and Guidelines 2015 (ref. 22). NA: not applicable. *The search was accomplished by the public domain software, ANNOVAR (http://annovar.openbioinformatics.org/). **Searched by The Human Genetic Variation Database (http://www.hgvd.genome.med.kyoto-u.ac.jp). ***Searched by dbSNP138 database using UCSC Genome Browser (https://genome.ucsc.edu/).
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