RESUMO
BACKGROUND: The etiology of multiple myeloma (MM) remains obscure, although reports of familial clustering have implicated both a host susceptibility factor and environmental effects. Here we describe the medical histories of members of a family prone to MM. METHODS: We developed a pedigree for an MM-prone family by using information obtained from a questionnaire. Protein immunoelectrophoresis of serum and urine from the proband and from 19 family members was performed to detect monoclonal immunoproteins. Peripheral blood obtained from the proband and from five relatives was subjected to standard cytogenetic studies to detect constitutional chromosomal abnormalities. Multifluor-fluorescence in situ hybridization (M-FISH) and standard FISH studies were performed on peripheral blood from the proband and from two other affected living relatives to determine their karyotypes and to detect clonal chromosomal abnormalities frequently seen in patients with MM. RESULTS: Within this family, a sibship of seven included three individuals (including the proband) with histologically verified MM and two individuals with a monoclonal gammopathy of unknown significance (MGUS), as determined by immunoelectrophoresis of serum and urine. This family also had members with acute lymphocytic leukemia, malignant melanoma, and prostate cancer. In the family members tested, we detected no constitutional chromosomal abnormality. None of the three individuals analyzed by FISH had a deletion of the retinoblastoma (Rb-1) locus, which is frequently deleted in patients with MM, and only one (the proband) had a translocation involving chromosomes 11 and 14, a clonal abnormality commonly seen in MM. CONCLUSION: The study of familial MM may provide insights into the pathogenesis and, ultimately, the control and prevention of MM and related disorders.
Assuntos
Mieloma Múltiplo/genética , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aberrações Cromossômicas , Cromossomos Humanos Par 11/ultraestrutura , Cromossomos Humanos Par 14/ultraestrutura , Feminino , Predisposição Genética para Doença , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/metabolismo , Proteínas do Mieloma/análise , Paraproteinemias/genética , Linhagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Neoplasias da Próstata/genética , Risco , Neoplasias Cutâneas/genética , Translocação GenéticaRESUMO
We have obtained and sequenced the coding sequence of the mouse cardiac alpha-myosin heavy chain (Myhc alpha) from the A/J, BALB/cByJ, C57BL/6J, and DBA/2J inbred mouse strains. Overlapping cDNA sequences were obtained using RNA-PCR and anchor-PCR techniques for these studies. In the A/J mouse strain, the full-length message is 5989 bp long and encodes for a protein consisting of 1938 amino acids (Mr 223,689). The protein deduced sequence of the A/J Myhc alpha was compared with corresponding sequences of human and rat Myhc alpha and beta. These results demonstrated that the mouse Myhc alpha is highly conserved and has maintained the alpha-isoform-specific divergent cluster observed in other Myhc alpha proteins. One difference was the loss of a glutamine at residue 1932, which is due to a change in an RNA splicing site sequence. Allelic variability was observed in both nucleotide and amino acid sequences among the four different inbred mouse strains and generally appears to be random in nature. Three of the nucleotide changes resulted in a different amino acid, while the remaining 46 were silent substitutions.