ABSTRACT
Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency with recurrent infections, IgA and IgE deficiency, and increased incidence of malignancies. The pathognomonic biological abnormalities consist of spontaneous chromosomal instability resulting in a high in vivo occurrence of cells with translocations, especially involving chromosomes 7 and 14, and a relative insensitivity of DNA replication in vitro to radiation exposure. We report on a patient with the biological hallmarks of AT but with atypical clinical manifestations. Although progressive cerebellar ataxia was present, the neurological picture was broader than that usually seen in AT and included peripheral polyneuropathy and spinal atrophy. On the other hand, telangiectasias, recurrent infections, malignancies, IgA deficiency, or other immunological abnormalities were not present. This illustrates that the clinical picture of AT is broad and nonspecific, and highlights the diagnostic value of cytogenetic analysis and studies of radioresistance of DNA synthesis.
Subject(s)
Ataxia Telangiectasia/diagnosis , Adult , Ataxia Telangiectasia/genetics , Chromosome Aberrations , Chromosomes, Human, Pair 14 , Chromosomes, Human, Pair 7 , DNA Replication/genetics , DNA Replication/radiation effects , Humans , In Vitro Techniques , Male , Radiation Tolerance/geneticsABSTRACT
Tricho-rhino-phalangeal (TRP) syndromes type I and II are caused by a defective gene located on chromosome 8q24.1. We report a family with 2 sibs affected with TRP type I in combination with an apparently balanced chromosome (8;18) translocation involving 8q24.11. It is very likely that the 8q24 translocation breakpoint is physically linked to the TRP gene(s), thereby facilitating future efforts to clone the TRP gene(s).
Subject(s)
Abnormalities, Multiple/genetics , Chromosomes, Human, Pair 18 , Chromosomes, Human, Pair 8 , Translocation, Genetic , Adult , Chromosome Banding , Female , Fingers/abnormalities , Hair/abnormalities , Humans , Infant , Karyotyping , Male , Nose/abnormalities , Osteochondrodysplasias/genetics , Pelvis/abnormalities , SyndromeABSTRACT
We describe two male sibs with mental retardation discordant for the fragile-X syndrome. In the younger sib, chromosome analysis under folate deprivation showed a fragile site at Xq27.3 in 12-46% of mitoses. In the older sib, however, repeated chromosome analyses (six different cultures with analysis of 50 mitoses each) under identical conditions could not detect any fragile-X site. Using DNA probes linked to the fragile-X gene, we found evidence that the two sibs inherited a different maternal X chromosome at Xq27.3. This excluded the presence of the fragile-X syndrome in the older sib with a probability of greater than 99%.
Subject(s)
Fragile X Syndrome/genetics , Intellectual Disability/genetics , Sex Chromosome Aberrations/genetics , Adult , Child , DNA/analysis , DNA Probes , Humans , Male , Pedigree , PhenotypeABSTRACT
In the pedigree reported here two apparently normal males may have transmitted the fragile X chromosome. Eighteen family members were examined cytogenetically. The fragile X was detected in a high percentage of cells from nine mentally retarded members of this family (six males and three females) and in one female obligate carrier. Four other obligate carriers showed no or only a few cells with the fragile X.
