PMID- 14708107
OWN - NLM
STAT- MEDLINE
DCOM- 20040728
LR  - 20200930
IS  - 1552-4825 (Print)
IS  - 1552-4833 (Electronic)
IS  - 1552-4825 (Linking)
VI  - 124A
IP  - 3
DP  - 2004 Jan 30
TI  - Independent de novo 22q11.2 deletions in first cousins with 
      DiGeorge/velocardiofacial syndrome.
PG  - 313-7
AB  - Deletions of chromosome 22q11.2 are found in the vast majority of patients with 
      DiGeorge/velocardiofacial syndrome (DGS/VCFS). This most frequent microdeletion 
      syndrome is estimated to occur in 1 in 4,000 live births. The majority of 
      deletions are de novo, with 10% or less inherited from an affected parent. Here, 
      we report two separate families with recurrence of a 22q11.2 deletion in first 
      cousins. In each family, unaffected siblings (brother and sister) had an affected 
      child. Fluorescence in situ hybridization (FISH) studies of the parents of each 
      affected child were normal and hence, relatives were not considered at an 
      increased risk for recurrence in another pregnancy. We used highly polymorphic 
      microsatellite repeat markers from within 22q11.2 to determine the parental 
      origin of each cousin's deletion and to assess whether parental germline 
      mosaicism for the 22q11.2 deletion might be a factor in these cases. This 
      analysis confirmed that in each case, the deletion occurred on a chromosome 22 
      derived from unrelated parents, consistent with independent de novo deletion 
      events. Thus, we concluded that germline mosaicism as the underlying mechanism 
      for affected cousins in these families was unlikely. Our findings underscore the 
      high frequency with which the 22q11.2 deletion occurs in the general population 
      and demonstrate the important role that PCR-based parental origin determination 
      can have in recurrence risk counselling. Furthermore, relatives of affected 
      individuals may benefit from genetic counselling and consider prenatal testing 
      for the 22q11.2 deletion in future pregnancies, despite a low recurrence risk.
CI  - Copyright 2003 Wiley-Liss, Inc.
FAU - Saitta, Sulagna C
AU  - Saitta SC
AD  - Division of Human Genetics and Molecular Biology, The Children's Hospital of 
      Philadelphia, Pennsylvania 19104, USA.
FAU - Harris, Stacy E
AU  - Harris SE
FAU - McDonald-McGinn, Donna M
AU  - McDonald-McGinn DM
FAU - Emanuel, Beverly S
AU  - Emanuel BS
FAU - Tonnesen, Melissa K
AU  - Tonnesen MK
FAU - Zackai, Elaine H
AU  - Zackai EH
FAU - Seitz, Suzanne C
AU  - Seitz SC
FAU - Driscoll, Deborah A
AU  - Driscoll DA
LA  - eng
GR  - P01-DC02027/DC/NIDCD NIH HHS/United States
GR  - M01 RR000240-410443/RR/NCRR NIH HHS/United States
GR  - P30-HD28815/HD/NICHD NIH HHS/United States
GR  - K08-HL04487/HL/NHLBI NIH HHS/United States
GR  - K08 HL004487/HL/NHLBI NIH HHS/United States
GR  - M01 RR000240/RR/NCRR NIH HHS/United States
GR  - P01 DC002027/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Med Genet A
JT  - American journal of medical genetics. Part A
JID - 101235741
SB  - IM
MH  - Abnormalities, Multiple/*genetics/pathology
MH  - Child, Preschool
MH  - *Chromosome Deletion
MH  - Chromosomes, Human, Pair 22/*genetics
MH  - Craniofacial Abnormalities/pathology
MH  - DiGeorge Syndrome/*genetics/pathology
MH  - Family Health
MH  - Female
MH  - Genotype
MH  - Haplotypes
MH  - Heart Defects, Congenital/*pathology
MH  - Humans
MH  - Male
MH  - Microsatellite Repeats
MH  - Pedigree
MH  - Syndrome
PMC - PMC2811370
MID - NIHMS160420
EDAT- 2004/01/07 05:00
MHDA- 2004/07/29 05:00
PMCR- 2010/01/26
CRDT- 2004/01/07 05:00
PHST- 2004/01/07 05:00 [pubmed]
PHST- 2004/07/29 05:00 [medline]
PHST- 2004/01/07 05:00 [entrez]
PHST- 2010/01/26 00:00 [pmc-release]
AID - 10.1002/ajmg.a.20421 [doi]
PST - ppublish
SO  - Am J Med Genet A. 2004 Jan 30;124A(3):313-7. doi: 10.1002/ajmg.a.20421.