Severe phenotype in an apparent homozygosity caused by a large deletion in the CFTR gene: a case report

BMC Research Notes

Giselda Maria Kalil Cabello⁵  Pedro Hernan Cabello⁴  Célia Regina Moutinho de Miranda Chaves³  Izabela Rocha Sad²  Laurinda Yoko Shinzato Higa²  Tania Wrobel Folescu²  Franklyn Enrique Samudio Acosta¹  Ana Carolina Proença Fonseca⁵  Raisa da Silva Martins⁵ 

[1] Laboratório de Parasitologia, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panama City, Panama;Departamento de Pneumologia, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;Departamento de Nutrição, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;Laboratório de Genética Humana, Universidade do Grande Rio, Unigranrio, Rio de Janeiro, Brazil;Laboratório de Genética Humana, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Pavilhão Leônidas Deane sala 611. CEP: 21040-360 Avenida Brasil 4365, Rio de Janeiro, Brazil

关键词: Brazilian patient;    Severe phenotype;    Large deletion;    Apparent homozygosis;    CFTR;    Cystic fibrosis;   

Others  :  1130002
DOI  :  10.1186/1756-0500-7-583

 received in 2014-03-08, accepted in 2014-08-26,  发布年份 2014

【 摘 要 】

Background

Over 1900 mutations have been identified in the cystic fibrosis conductance transmembrane regulator gene, including single nucleotide substitutions, insertions, and deletions. Unidentified mutations may still lie in introns or in regulatory regions, which are not routinely investigated, or in large genomic deletions, which are not revealed by conventional molecular analysis. The apparent homozygosity for a rare, cystic fibrosis conductance transmembrane regulator mutation screened by standard molecular analysis should be further investigated to confirm if the mutation is in fact homozygous. We describe a patient presenting with an apparent homozygous S4X mutation.

Case presentation

A 13-year-old female patient of African descent with clinical symptoms of classic cystic fibrosis and a positive sweat test (97 mEq/L, diagnosed at age 3 years) presented with pancreatic insufficiency and severe pulmonary symptoms (initial lung colonization with Pseudomonas aeruginosa at age 4 years; forced vital capacity: 69%; forced expiratory volume: 51%; 2011). Furthermore, she developed severe acute lung disease and recurrent episodes of dehydration requiring hospitalization. The girl carried the CFTR mutation S4X in apparent homozygosity. However, further analysis revealed a large deletion in the second allele that included the region of the mutation. The deletion that we describe includes nucleotides 120–142, which correspond to a loss of 23 nucleotides that abolishes the normal translation initiation codon.

Conclusion

This study reiterates the view that large, cystic fibrosis conductance transmembrane regulator deletions are an important cause of severe cystic fibrosis and emphasizes the importance of including large deletions/duplications in cystic fibrosis conductance transmembrane regulator diagnostic tests.

【 授权许可】

   
2014 da Silva Martins et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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