PMID- 26174853
OWN - NLM
STAT- MEDLINE
DCOM- 20160303
LR  - 20181113
IS  - 1755-8794 (Electronic)
IS  - 1755-8794 (Linking)
VI  - 8
DP  - 2015 Jul 15
TI  - Haploinsufficiency and triploinsensitivity of the same 6p25.1p24.3 region in a 
      family.
PG  - 38
LID - 10.1186/s12920-015-0113-1 [doi]
LID - 38
AB  - BACKGROUND: Chromosome 6pter-p24 deletion syndrome (OMIM #612582) is a recognized 
      chromosomal disorder. Most of the individuals with this syndrome carry a terminal 
      deletion of the short arm of chromosome 6 (6p) with a breakpoint within the 
      6p25.3p23 region. An approximately 2.1 Mb terminal region has been reported to be 
      responsible for some major features of the syndrome. The phenotypic contributions 
      of other deleted regions are unknown. Interstitial deletions of the region are 
      uncommon, and reciprocal interstitial duplication in this region is extremely 
      rare. CASE PRESENTATION: We present a family carrying an interstitial deletion 
      and its reciprocal duplication within the 6p25.1p24.3 region. The deletion is 
      5.6 Mb in size and was detected by array comparative genomic hybridization (aCGH) 
      in a 26-month-old female proband who presented speech delay and mild growth 
      delay, bilateral conductive hearing loss and dysmorphic features. Array CGH 
      studies of her family members detected an apparently mosaic deletion of the same 
      region in the proband's mildly affected mother, but a reciprocal interstitial 
      duplication in her phenotypically normal brother. Further chromosomal and 
      fluorescence in situ hybridization (FISH) analyses revealed that instead of a 
      simple mosaic deletion of 6p25.1p24.3, the mother actually carries three cell 
      populations in her peripheral blood, including a deletion (~70 %), a duplication 
      (~8 %) and a normal (~22 %) populations. Therefore, both the deletion and 
      duplication seen in the siblings were apparently inherited from the mother. 
      CONCLUSIONS: Interstitial deletion within the 6p25.1p24.3 region and its 
      reciprocal duplication may co-exist in the same individual and/or family due to 
      mitotic unequal sister chromatid exchange. While the deletion causes phenotypes 
      reportedly associated with the chromosome 6pter-p24 deletion syndrome, the 
      reciprocal duplication may have no or minimal phenotypic effect, suggesting 
      possible triploinsensitivity of the same region. In addition, the cells with the 
      duplication may compensate the phenotypic effect of the cells with the deletion 
      in the same individual as implied by the maternal karyotype and her mild 
      phenotype. Chromosomal and FISH analyses are essential to verify abnormal 
      cytogenomic array findings.
FAU - Qi, Zhongxia
AU  - Qi Z
AD  - Department of Laboratory Medicine, University of California San Francisco, San 
      Francisco, CA, 94107, USA. Zhongxia.Qi@ucsf.edu.
FAU - Jeng, Linda Jo Bone
AU  - Jeng LJ
AD  - Departments of Medicine, Pediatrics and Pathology, Program for Personalized and 
      Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, 
      21201, USA. LJeng@som.umaryland.edu.
FAU - Slavotinek, Anne
AU  - Slavotinek A
AD  - Department of Pediatrics, University of California San Francisco, San Francisco, 
      CA, 94143, USA. SlavotiA@ucsf.edu.
FAU - Yu, Jingwei
AU  - Yu J
AD  - Department of Laboratory Medicine, University of California San Francisco, San 
      Francisco, CA, 94107, USA. Jingwei.Yu@ucsf.edu.
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20150715
PL  - England
TA  - BMC Med Genomics
JT  - BMC medical genomics
JID - 101319628
RN  - Chromosome 6pter-P24 Deletion Syndrome
SB  - IM
MH  - Adult
MH  - Child, Preschool
MH  - Chromosome Deletion
MH  - Chromosome Duplication
MH  - Chromosomes, Human, Pair 6/*genetics
MH  - Comparative Genomic Hybridization
MH  - Eye Abnormalities/genetics
MH  - Female
MH  - Genotype
MH  - *Haploinsufficiency
MH  - Hearing Loss/genetics
MH  - Heart Defects, Congenital/genetics
MH  - Humans
MH  - Hypertelorism/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Pedigree
MH  - Phenotype
MH  - Pregnancy
PMC - PMC4502905
EDAT- 2015/07/16 06:00
MHDA- 2016/03/05 06:00
PMCR- 2015/07/15
CRDT- 2015/07/16 06:00
PHST- 2014/10/17 00:00 [received]
PHST- 2015/07/03 00:00 [accepted]
PHST- 2015/07/16 06:00 [entrez]
PHST- 2015/07/16 06:00 [pubmed]
PHST- 2016/03/05 06:00 [medline]
PHST- 2015/07/15 00:00 [pmc-release]
AID - 10.1186/s12920-015-0113-1 [pii]
AID - 113 [pii]
AID - 10.1186/s12920-015-0113-1 [doi]
PST - epublish
SO  - BMC Med Genomics. 2015 Jul 15;8:38. doi: 10.1186/s12920-015-0113-1.