title: Mental retardation, congenital heart malformation, and myelodysplasia in a patient with a complex chromosomal rearrangement involving the critical region 21q22.
abstract: The region 21q22 is considered crucial for the pathogenesis of both Down syndrome (DS) and the partial monosomy 21q syndrome. Haploinsufficiency of the RUNX-1 gene, mapping at 21q22 is responsible for a platelet disorder and causes predisposition to myelodysplastic syndrome (MDS). We describe a 3-year-old girl with mental retardation, congenital heart malformation, and subtle dysmorphic facial features. The patient developed thrombocytopenia when she was 2 years old. Bone marrow smear led to the diagnosis of myelodysplasia. Prenatal karyotyping had shown chromosome 21 pericentric inversion. Postnatally the array-CGH revealed duplication at bands 21q11.2-21q21.1 and a simultaneous deletion involving the region 21q22.13-21q22.3. RUNX-1 mRNA levels analyzed in patient's skin fibroblasts were reduced. In this child the monosomy of the region 21q22 likely had the main role in determining the phenotype. Although the RUNX-1 gene is localized outside the deleted region, we speculate that RUNX-1 reduced expression, is probably due to the deletion of regulatory factors and caused the hematologic disorder in the patient. The present report underlines also the importance of array-CGH in characterizing patients with a complex phenotype.
authors.affiliation: Department of Paediatrics, "Federico II" University, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Melis
authors.forename: Rita
authors.initials: R
authors.lastname: Genesio
authors.forename: Gerarda
authors.initials: G
authors.lastname: Cappuccio
authors.forename: Virginia
authors.initials: V
authors.lastname: MariaGinocchio
authors.forename: Roberto Della
authors.initials: RD
authors.lastname: Casa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Menna
authors.forename: Salvatore
authors.initials: S
authors.lastname: Buffardi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Poggi
authors.forename: Anna
authors.initials: A
authors.lastname: Leszle
authors.forename: Floriana
authors.initials: F
authors.lastname: Imperati
authors.forename: Massimo
authors.initials: M
authors.lastname: Carella
authors.forename: Antonella
authors.initials: A
authors.lastname: Izzo
authors.forename: Ennio
authors.initials: E
authors.lastname: Del Giudice
authors.forename: Lucio
authors.initials: L
authors.lastname: Nitsch
authors.forename: Generoso
authors.initials: G
authors.lastname: Andria
mesh_terms: D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D014314:Trisomy
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D012333:RNA, Messenger