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.

Mental retardation, congenital heart malformation, and myelodysplasia in a patient with a complex chromosomal rearrangement involving the critical region 21q22 / Melis, Daniela; Genesio, Rita; Cappuccio, Gerarda; Mariaginocchio, Virginia; DELLA CASA, Roberto; Menna, Giuseppe; Buffardi, Salvatore; Poggi, Vincenzo; Leszle, Anna; Imperati, Floriana; Carella, Massimo; Izzo, Antonella; DEL GIUDICE, Ennio; Nitsch, Lucio; Andria, Generoso. - In: AMERICAN JOURNAL OF MEDICAL GENETICS. PART A. - ISSN 1552-4825. - 155:7(2011), pp. 1697-1705. [10.1002/ajmg.a.33976]

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

Gerarda Cappuccio;DELLA CASA, ROBERTO;IZZO, ANTONELLA;DEL GIUDICE, ENNIO;NITSCH, LUCIO;ANDRIA, GENEROSO
2011

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.
2011
Mental retardation, congenital heart malformation, and myelodysplasia in a patient with a complex chromosomal rearrangement involving the critical region 21q22 / Melis, Daniela; Genesio, Rita; Cappuccio, Gerarda; Mariaginocchio, Virginia; DELLA CASA, Roberto; Menna, Giuseppe; Buffardi, Salvatore; Poggi, Vincenzo; Leszle, Anna; Imperati, Floriana; Carella, Massimo; Izzo, Antonella; DEL GIUDICE, Ennio; Nitsch, Lucio; Andria, Generoso. - In: AMERICAN JOURNAL OF MEDICAL GENETICS. PART A. - ISSN 1552-4825. - 155:7(2011), pp. 1697-1705. [10.1002/ajmg.a.33976]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/576225
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