PMID- 26523152
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151102
LR  - 20200930
IS  - 1755-8166 (Print)
IS  - 1755-8166 (Electronic)
IS  - 1755-8166 (Linking)
VI  - 8
DP  - 2015
TI  - Characterization of intragenic tandem duplication in the PAFAH1B1 gene leading to 
      isolated lissencephaly sequence.
PG  - 84
LID - 10.1186/s13039-015-0186-8 [doi]
LID - 84
AB  - BACKGROUND: Genetic aberrations in PAFAH1B1 result in isolated lissencephaly 
      sequence (ILS), a neuronal migration disorder associated with severe mental 
      retardation and intractable epilepsy. Approximately 60 % of patients with ILS 
      show a 17p13.3 deletion or an intragenic variation of PAFAH1B1 that can be 
      identified by fluorescence in situ hybridization (FISH) analysis or gene 
      sequencing. Using multiplex ligation-dependent probe amplification (MLPA), 40-80 
      % of the remaining patients show small genomic deletions or duplications of 
      PAFAH1B1. The intragenic duplications within PAFAH1B1 are predicted to abolish 
      the PAFAH1B1 function, although a detailed characterization of the duplication 
      regions have not been reported. RESULTS: Here we describe a female patient with 
      ILS occurring predominantly in the posterior brain regions. MLPA was used to 
      identify a small duplication within PAFAH1B1. This result was confirmed by 
      array-based comparative genomic hybridization analysis, revealing a duplication 
      of the 29-kb region encompassing putative regulatory elements and exon 2 of 
      PAFAH1B1. The region was characterized as an intragenic tandem duplication by 
      sequencing, revealing a 28-bp microhomology sequence at the breakpoint junctions. 
      Parental genetic testing confirmed that the tandem duplication occurred de novo. 
      Reverse transcription-PCR on RNA extracted from peripheral blood leukocytes 
      revealed that the expression level of PAFAH1B1 decreased to that in a patient 
      with Miller-Dieker syndrome, a contiguous gene-deletion disorder characterized by 
      classical lissencephaly and a facial dysmorphism. CONCLUSIONS: This study 
      expanded the spectrum of PAFAH1B1 variants and identified a unique genomic 
      architecture including microhomology sequences in PAFAH1B1 underlying an 
      intragenic tandem duplication leading to ILS.
FAU - Takahashi, Satoru
AU  - Takahashi S
AD  - Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 
      Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 Japan.
FAU - Tanaka, Ryosuke
AU  - Tanaka R
AD  - Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 
      Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 Japan.
FAU - Okano, Satomi
AU  - Okano S
AD  - Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 
      Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 Japan.
FAU - Okayama, Akie
AU  - Okayama A
AD  - Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 
      Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 Japan.
FAU - Suzuki, Nao
AU  - Suzuki N
AD  - Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 
      Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 Japan.
FAU - Azuma, Hiroshi
AU  - Azuma H
AD  - Department of Pediatrics, Asahikawa Medical University, 2-1-1-1 
      Midorigaoka-Higashi, Asahikawa, Hokkaido 078-8510 Japan.
LA  - eng
PT  - Case Reports
DEP - 20151031
PL  - England
TA  - Mol Cytogenet
JT  - Molecular cytogenetics
JID - 101317942
PMC - PMC4628255
OTO - NOTNLM
OT  - Duplication
OT  - Lissencephaly
OT  - Microhomology
OT  - Neuronal migration
OT  - PAFAH1B1
EDAT- 2015/11/03 06:00
MHDA- 2015/11/03 06:01
PMCR- 2015/10/31
CRDT- 2015/11/03 06:00
PHST- 2015/08/03 00:00 [received]
PHST- 2015/10/17 00:00 [accepted]
PHST- 2015/11/03 06:00 [entrez]
PHST- 2015/11/03 06:00 [pubmed]
PHST- 2015/11/03 06:01 [medline]
PHST- 2015/10/31 00:00 [pmc-release]
AID - 186 [pii]
AID - 10.1186/s13039-015-0186-8 [doi]
PST - epublish
SO  - Mol Cytogenet. 2015 Oct 31;8:84. doi: 10.1186/s13039-015-0186-8. eCollection 
      2015.