RESUMO
Hb Bronovo [α103(G10)HisâLeu, HBA2: c.311A>T] is an α-globin variant that interferes with and decreases binding efficiency to α hemoglobin (Hb) stabilizing protein (AHSP), a chaperone molecule. The histidine residue at position 103 is integral to the AHSP hydrogen bond formation where disruption results in an increased quantity of cytotoxic free α-globin chains, thereby creating a similar pathophysiology as ß-thalassemia (ß-thal). We report a family with Hb Bronovo, including a homozygous proband, which resulted from maternal uniparental disomy (UPD). Although not detected by routine studies in previous reports, the variant protein is visible by intact mass spectrometry (MS).
Assuntos
Alelos , Hemoglobinas Anormais/genética , Homozigoto , Mutação , alfa-Globinas/genética , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Substituição de Aminoácidos , Pré-Escolar , Mapeamento Cromossômico , Análise Mutacional de DNA , Feminino , Testes Genéticos , Heterozigoto , Humanos , Padrões de Herança , Masculino , Herança Materna , LinhagemRESUMO
Li-Fraumeni syndrome is an autosomal dominant cancer syndrome characterized by pathogenic variants in the TP53 gene on chromosome 17. The most common cancers in Li-Fraumeni kindreds include sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma. We report a 9-month-old male who was diagnosed with an adrenocortical tumor and later found to harbor a novel TP53 c.559 G > C germline variant, resulting in p.Gly187Arg. Family history included early-onset breast cancer in his paternal grandmother and paternal great-grandfather, as well as colon cancer at age 31 in a paternal cousin. The same TP53 variant was later confirmed in his paternal grandmother. Based on this information, his father (age 28, obligate carrier for the variant) was referred for colonoscopic screening and found to have multiple adenomatous polyps. This previously undescribed variant lies at an exon/intron boundary and is predicted to decrease splice site efficiency with resulting altered splicing or exon skipping. Our patient's family history provides limited evidence that this variant is a cause of Li-Fraumeni syndrome.
Assuntos
Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/genética , Mutação em Linhagem Germinativa , Síndrome de Li-Fraumeni/genética , Proteína Supressora de Tumor p53/genética , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/patologia , Humanos , Lactente , Síndrome de Li-Fraumeni/patologia , Masculino , Linhagem , PrognósticoAssuntos
Transtornos Cromossômicos/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 18 , Feminino , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológicoRESUMO
In this article, a father and son describe the experience of childhood leukemia treatment and its aftermath with the unique perspective of a parent who is also a pediatric oncologist. An illness that began with an apparently favorable prognosis was transformed by an early relapse, followed by unexpected complications and difficult treatment decisions. Despite unfavorable statistics, the son is a long-term survivor with an overall excellent quality of life, despite several late events and effects. His father, in the meantime, gained insights that now inform his own practice.