title: Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb.
abstract: Diamond-Blackfan anaemia (DBA; MIM#205900) is a rare disorder manifested as a pure red-cell aplasia in the neonatal period or in infancy. The clinical hallmark of DBA is a selective decrease in erythroid precursors and anaemia. Other lineages are usually normal and the peripheral white blood cell count is normal. In approximately one-third of cases, the disease is associated with a wide variety of congenital anomalies and malformations. Most cases are sporadic, but 10-20% of them follow a recessive or a dominant inheritance pattern. A female with DBA and a chromosomal translocation involving chromosome 19q was recently identified. We undertook a linkage analysis with chromosome 19 markers in multiplex DBA families of Swedish, French, Dutch, Arabic and Italian origin. Significant linkage to chromosome 19q13 was established for dominant and recessive inherited DBA with a peak lod score at D19S197 (Zmax = 7.08, theta = 0.00). Within this region, a submicroscopic de novo deletion of 3.3 Mb was identified in a patient with DBA. The deletion coincides with the translocation break-point and, together with key recombinations, restricts the DBA gene to a 1.8-Mb region. The results suggest that, despite its clinical heterogeneity, DBA is genetically homogeneous for a gene in 19q13.
authors.affiliation: Department of Clinical Genetics, Uppsala University Children's Hospital, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Gustavsson
authors.forename: T N
authors.initials: TN
authors.lastname: Willing
authors.forename: A
authors.initials: A
authors.lastname: van Haeringen
authors.forename: G
authors.initials: G
authors.lastname: Tchernia
authors.forename: I
authors.initials: I
authors.lastname: Dianzani
authors.forename: M
authors.initials: M
authors.lastname: Donnér
authors.forename: G
authors.initials: G
authors.lastname: Elinder
authors.forename: J I
authors.initials: JI
authors.lastname: Henter
authors.forename: P G
authors.initials: PG
authors.lastname: Nilsson
authors.forename: L
authors.initials: L
authors.lastname: Gordon
authors.forename: G
authors.initials: G
authors.lastname: Skeppner
authors.forename: L
authors.initials: L
authors.lastname: van't Veer-Korthof
authors.forename: A
authors.initials: A
authors.lastname: Kreuger
authors.forename: N
authors.initials: N
authors.lastname: Dahl
mesh_terms: D000328:Adult; D015220:Calcium Channels / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D002272:Carcinoembryonic Antigen / Q000235:genetics; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004268:DNA-Binding Proteins / Q000235:genetics; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats; D009124:Muscle Proteins / Q000235:genetics; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel; D016212:Transforming Growth Factor beta / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D002272:Carcinoembryonic Antigen; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D016212:Transforming Growth Factor beta; D000076105:X-ray Repair Cross Complementing Protein 1; C068969:HRC protein, human