PMID- 38256266
OWN - NLM
STAT- MEDLINE
DCOM- 20240124
LR  - 20240131
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 25
IP  - 2
DP  - 2024 Jan 18
TI  - Reanalysis of Trio Whole-Genome Sequencing Data Doubles the Yield in Autism 
      Spectrum Disorder: De Novo Variants Present in Half.
LID - 10.3390/ijms25021192 [doi]
LID - 1192
AB  - Autism spectrum disorder (ASD) is a common condition with lifelong implications. 
      The last decade has seen dramatic improvements in DNA sequencing and related 
      bioinformatics and databases. We analyzed the raw DNA sequencing files on the 
      Variantyx((R)) bioinformatics platform for the last 50 ASD patients evaluated with 
      trio whole-genome sequencing (trio-WGS). "Qualified" variants were defined as 
      coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV), 
      additionally, were present in genes directly linked to ASD and matched clinical 
      correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) 
      cases with heterozygous de novo and 10 (20%) with inherited variants. De novo 
      variants in genes directly associated with ASD were far more likely to be 
      Qualifying than non-Qualifying versus a control group of genes (p = 0.0002), 
      validating that most are indeed disease related. Sequence reanalysis increased 
      diagnostic yield from 28% to 68%, mostly through inclusion of de novo PDVs in 
      genes not yet reported as ASD associated. Thirty-three subjects (66%) had 
      treatment recommendation(s) based on DNA analyses. Our results demonstrate a high 
      yield of trio-WGS for revealing molecular diagnoses in ASD, which is greatly 
      enhanced by reanalyzing DNA sequencing files. In contrast to previous reports, de 
      novo variants dominate the findings, mostly representing novel conditions. This 
      has implications to the cause and rising prevalence of autism.
FAU - Bar, Omri
AU  - Bar O
AD  - NeurAbilities Healthcare(R), Voorhees, NJ 08043, USA.
FAU - Vahey, Elizabeth
AU  - Vahey E
AD  - NeurAbilities Healthcare(R), Voorhees, NJ 08043, USA.
FAU - Mintz, Mark
AU  - Mintz M
AD  - NeurAbilities Healthcare(R), Voorhees, NJ 08043, USA.
FAU - Frye, Richard E
AU  - Frye RE
AUID- ORCID: 0000-0003-4442-2937
AD  - Autism Discovery and Treatment Foundation, Phoenix, AZ 85050, USA.
FAU - Boles, Richard G
AU  - Boles RG
AD  - NeurAbilities Healthcare(R), Voorhees, NJ 08043, USA.
AD  - NeuroNeeds(R), Old Lyme, CT 06371, USA.
LA  - eng
GR  - none/none/
PT  - Journal Article
DEP - 20240118
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
SB  - IM
MH  - Humans
MH  - *Autism Spectrum Disorder/genetics
MH  - Whole Genome Sequencing
MH  - Sequence Analysis, DNA
MH  - *Autistic Disorder
MH  - Computational Biology
PMC - PMC10816071
OTO - NOTNLM
OT  - DNA sequencing
OT  - autism
OT  - diagnostic yield
OT  - novel disorders
COIS- R.B. is an officer and receives equity from NeuroNeeds((R)), a company that 
      produces dietary supplements for neurological conditions. The remaining authors 
      declare that the research was conducted in the absence of any commercial or 
      financial relationships that could be construed as a potential conflict of 
      interests.
EDAT- 2024/01/23 06:42
MHDA- 2024/01/24 06:43
PMCR- 2024/01/18
CRDT- 2024/01/23 01:13
PHST- 2023/12/24 00:00 [received]
PHST- 2024/01/14 00:00 [revised]
PHST- 2024/01/16 00:00 [accepted]
PHST- 2024/01/24 06:43 [medline]
PHST- 2024/01/23 06:42 [pubmed]
PHST- 2024/01/23 01:13 [entrez]
PHST- 2024/01/18 00:00 [pmc-release]
AID - ijms25021192 [pii]
AID - ijms-25-01192 [pii]
AID - 10.3390/ijms25021192 [doi]
PST - epublish
SO  - Int J Mol Sci. 2024 Jan 18;25(2):1192. doi: 10.3390/ijms25021192.