RESUMO
We report on a 22-year-old woman with features of osteogenesis imperfecta (OI), tricho-dento-osseous (TDO) syndrome and intellectual disability. Whole genome oligonucleotide microarray analysis revealed a copy number gain of 3 Mb in 7q32.3-q33 and a loss of 3.4 Mb in 17q21.33-q22. FISH analysis showed that the third copy of 7q32 was inserted into the long arm of one chromosome 17, exactly in the region 17q21.33-q22 that was deleted. The maternal uncle presented with clinical features similar to the proposita and had the same chromosomal anomalies. The mother of the proposita and two other family members were balanced carriers of this rearrangement, interpreted as an interchromosomal reciprocal insertion. Reciprocal insertion/four-break rearrangement is a very rare chromosomal event. The deleted region on chromosome 17 contains 39 genes, including COL1A1 and DLX3 involved in OI and TDO syndrome respectively. The CACNA1G gene on the deleted segment of chromosome 17 may be a good candidate gene to explain the intellectual impairment. © 2013 Wiley Periodicals, Inc.
Assuntos
Anormalidades Craniofaciais/genética , Hipoplasia do Esmalte Dentário/genética , Doenças do Cabelo/genética , Deficiência Intelectual/genética , Osteogênese Imperfeita/genética , Duplicação Cromossômica , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 7 , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Hibridização Genômica Comparativa , Anormalidades Craniofaciais/diagnóstico , Hipoplasia do Esmalte Dentário/diagnóstico , Feminino , Doenças do Cabelo/diagnóstico , Proteínas de Homeodomínio/genética , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutagênese Insercional , Osteogênese Imperfeita/diagnóstico , Linhagem , Fenótipo , Deleção de Sequência , Síndrome , Fatores de Transcrição/genética , Adulto JovemRESUMO
Ocular coloboma, heart malformation, choanal atresia, retardation of growth and/or development, genital hypoplasia, and ear anomalies associated with deafness (CHARGE) syndrome is a rare, usually sporadic, autosomal dominant disorder, caused by mutations within the CHD7 (chromodomain helicase DNA-binding protein 7) gene, in nearly 70% of cases. Because human CHD7 is relatively large (38 exons encoding a 300-kDa protein), genetic analysis requires cost-effective and time-consuming techniques. Herein, we propose an alternative screening method to quickly detect CHD7 mutations using mainly denaturing high-performance liquid chromatography. The entire coding region with exon-intron boundaries was amplified under the same experimental conditions. Each amplicon of the same CHD7 region was subjected to denaturing high-performance liquid chromatography analysis, and resulting chromatograms were compared within small series of patients. Because a CHD7 mutation differs generally from one patient to another, corresponding chromatograms exhibited a unique pattern that is significantly different from common polymorphisms. Only amplicons exhibiting a unique profile were subjected to DNA sequencing analysis. Intragenic rearrangements were investigated with only nine multiplex PCRs. In conclusion, using our protocol, we can quickly detect the right containing mutation amplicon and we provide a robust, rapid, and cheaper method to screen CHD7 microrearrangements or an entire deletion.