Mental retardation, congenital heart malformation, and myelodysplasia in a patient with a complex chromosomal rearrangement involving the critical region 21q22

Daniela Melis, Rita Genesio, Gerarda Cappuccio, Virginia Mariaginocchio, Roberto Della Casa, Giuseppe Menna, Salvatore Buffardi, Vincenzo Poggi, Anna Leszle, Floriana Imperati, Massimo Carella, Antonella Izzo, Ennio Del Giudice, Lucio Nitsch, Generoso Andria

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1697-1705
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Volume155
Issue number7
DOIs
Publication statusPublished - Jul 2011

Keywords

  • Array-CGH
  • Invdupdel(21)
  • Monosomy 21q22
  • Myelodysplastic syndrome
  • Trisomy 21q

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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