Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/13683
A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review
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eISSN: 1471-2350
WOS ID: 000267862000001
Scopus EID: 2-s2.0-67649196114
PMID: 19490635
Embase PUI: L354838264
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2009-06-02Document type
research articleCitation
Fernandez L, Nevado J, Santos F, Heine-Suner D, Martinez-Glez Vi, Garcia-Minaur S, et al. A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review. BMC Med Genet. 2009 Jun 02;10:48.Abstract
Background: Individuals affected with DiGeorge and Velocardiofacial syndromes present with both phenotypic diversity and variable expressivity. The most frequent clinical features include conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial dysmorphism. The etiology in most patients is a 3 Mb recurrent deletion in region 22q11.2. However, cases of infrequent deletions and duplications with different sizes and locations have also been reported, generally with a milder, slightly different phenotype for duplications but with no clear genotype-phenotype correlation to date. Methods: We present a 7 month-old male patient with surgically corrected ASD and multiple VSDs, and dysmorphic facial features not clearly suggestive of 22q11.2 deletion syndrome, and a newborn male infant with cleft lip and palate and upslanting palpebral fissures. Karyotype, FISH, MLPA, microsatellite markers segregation studies and SNP genotyping by array-CGH were performed in both patients and parents. Results: Karyotype and FISH with probe N25 were normal for both patients. MLPA analysis detected a partial de novo 1.1 Mb deletion in one patient and a novel partial familial 0.4 Mb duplication in the other. Both of these alterations were located at a distal position within the commonly deleted region in 22q11.2. These rearrangements were confirmed and accurately characterized by microsatellite marker segregation studies and SNP array genotyping. Conclusion: The phenotypic diversity found for deletions and duplications supports a lack of genotype-phenotype correlation in the vicinity of the LCRC-LCRD interval of the 22q11.2 chromosomal region, whereas the high presence of duplications in normal individuals supports their role as polymorphisms. We suggest that any hypothetical correlation between the clinical phenotype and the size and location of these alterations may be masked by other genetic and/or epigenetic modifying factors.
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https://dx.doi.org/10.1186/1471-2350-10-48MeSH
Gene DuplicationNucleic Acid Amplification Techniques
Chromosome Deletion
Humans
Heart Septal Defects, Ventricular
Karyotyping
Infant
Polymorphism, Single Nucleotide
Chromosomes, Human, Pair 22
Heart Septal Defects, Atrial
Male
Gene Dosage
In Situ Hybridization, Fluorescence
Syndrome
DeCS
Polimorfismo de Nucleótido SimpleSíndrome
Hibridación Fluorescente in Situ
Duplicación de Gen
Dosificación de Gen
Lactante
Masculino
Técnicas de Amplificación de Ácido Nucleico
Defectos del Tabique Interventricular
Cromosomas Humanos Par 22
Defectos del Tabique Interatrial
Deleción Cromosómica
Humanos
Cariotipificación