title: Positional mapping of loci in the DiGeorge critical region at chromosome 22q11 using a new marker (D22S183).
abstract: The majority of patients with DiGeorge syndrome (DGS) and velo-cardio-facial syndrome (VCFS) and a minority of patients with non-syndromic conotruncal heart defects are hemizygous for a region of chromosome 22q11. The chromosomal region that is commonly deleted is larger than 2 Mb. It has not been possible to narrow the smallest region of overlap (SRO) of the deletions to less than ca 500 kb, which suggests that DGS/VCFS might be a contiguous gene syndrome. The saturation cloning of the SRO is being carried out, and one gene (TUPLE1) has been identified. By using a cosmid probe (M51) and fluorescence in situ hybridization, we show here that the anonymous DNA marker locus D22S183 is within the SRO, between TUPLE1 and D22S75 (probe N25). A second locus with weak homology to D22S183, recognized by cosmid M56, lies immediately outside the common SRO of the DGS and VCFS deletions, but inside the SRO of the DGS deletions. D22S183 sequences are strongly conserved in primates and weaker hybridizing signals are found in DNA of other mammalian species; no transcripts are however detected in polyA+ RNA from various adult human organs. Probe M51 allows fast reliable screening for 22q11 deletions using fluorescence in situ hybridization. A deletion was found in 11 out of 12 DGS patients and in 3 out of 7 VCFS patients. Two patients inherited the deletion from a parent with mild (atypical) symptoms.
authors.affiliation: Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
authors.forename: M P
authors.initials: MP
authors.lastname: Mulder
authors.forename: M
authors.initials: M
authors.lastname: Wilke
authors.forename: A
authors.initials: A
authors.lastname: Langeveld
authors.forename: L G
authors.initials: LG
authors.lastname: Wilming
authors.forename: A
authors.initials: A
authors.lastname: Hagemeijer
authors.forename: E
authors.initials: E
authors.lastname: van Drunen
authors.forename: E C
authors.initials: EC
authors.lastname: Zwarthoff
authors.forename: P H
authors.initials: PH
authors.lastname: Riegman
authors.forename: W H
authors.initials: WH
authors.lastname: Deelen
authors.forename: A M
authors.initials: AM
authors.lastname: van den Ouweland
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D015139:Blotting, Southern; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003360:Cosmids; D004062:DiGeorge Syndrome / Q000235:genetics*; D005145:Face / Q000002:abnormalities; D005260:Female; D005819:Genetic Markers; D015698:Genomic Library; D006330:Heart Defects, Congenital / Q000235:genetics; D056488:Histone Chaperones; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D010375:Pedigree; D017384:Sequence Deletion; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D005819:Genetic Markers; C086057:HIRA protein, human; D056488:Histone Chaperones; D014157:Transcription Factors