Subject(s)
Cutis Laxa/congenital , Cutis Laxa/genetics , Genes, Recessive , Mutation , Pyrroline Carboxylate Reductases/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Child, Preschool , Cutis Laxa/diagnosis , Female , Humans , Infant , Infant, Newborn , Male , Pedigree , Phenotype , delta-1-Pyrroline-5-Carboxylate ReductaseSubject(s)
Aldehyde Oxidoreductases/genetics , Mutation , RNA Splice Sites/genetics , Sjogren-Larsson Syndrome/genetics , Adolescent , Adult , Base Sequence , Child , Child, Preschool , Female , Genetic Testing/methods , Humans , Male , Sjogren-Larsson Syndrome/diagnosis , Sjogren-Larsson Syndrome/pathologyABSTRACT
An 8-year-old girl with growth deficiency, mental retardation, unusual facies and hypertrichosis is described. The case is compared with one described by Wiedemann et al. [(1989) Atlas of Clinical Syndromes, 2nd ed. London: Wolfe Publishing pp. 198-199].
Subject(s)
Facial Bones/abnormalities , Facies , Growth Disorders/pathology , Hypertrichosis/pathology , Intellectual Disability/pathology , Child , Female , HumansABSTRACT
We report on three sibs presenting with spondylocarpotarsal synostosis, short-trunk dwarfism of postnatal onset, scoliosis, unsegmented thoracic vertebrae with unilateral bar, and carpal bone fusion. Tarsal bone fusion and dental abnormalities were noted in some of them, indicating pleiotropy and intrafamilial variability. Lens opacities, rarefaction of retinal pigmentation, and narrowing of retinal vessels, detected in two patients, are findings that have not been described to date in this condition.
Subject(s)
Carpal Bones/abnormalities , Eye Abnormalities/diagnosis , Spine/abnormalities , Synostosis/diagnosis , Tarsal Bones/abnormalities , Abnormalities, Multiple/diagnosis , Adolescent , Adult , Carpal Bones/diagnostic imaging , Chromosome Banding , Dwarfism/diagnosis , Family Health , Female , Humans , Male , Pedigree , Radiography , Spine/diagnostic imaging , Tarsal Bones/diagnostic imagingABSTRACT
Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA) is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%), 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6% in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30% of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.
Subject(s)
Mutation/genetics , Spinocerebellar Degenerations/genetics , Adolescent , Adult , Brazil , Child , Chromosome Aberrations/genetics , Chromosome Disorders , DNA Mutational Analysis , Genes, Dominant , Humans , Machado-Joseph Disease/genetics , Middle AgedABSTRACT
The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of late onset neurodegenerative disorders. To date, seven different genes causing autosomal dominant SCA have been mapped: SCA1, SCA2, Machado-Joseph disease (MJD)SCA3, SCA4, SCA5, SCA7 and dentatorubropallidoluysian atrophy (DRPLA). Expansions of an unstable trinucleotide CAG repeat cause three of these disorders: SCA1, MJD/SCA3 and DRPLA. We studied one Brazilian family segregating an autosomal dominant type of SCA. A total of ten individuals were examined and tested for the presence of the SCA1, MJD and DRPLA mutations. Three individuals, one male, and two females, were considered affected based on neurological examination; ages at onset were 32, 36 and 41 years. The first complaint in all three patients was gait ataxia which progressed slowly over the years. Six individuals showed one allele containing an expanded CAG repeat in the SCA1 gene. The mean size of the expanded allele was 48.2 CAG units. Instability of the expanded CAG tract was seen in the two transmissions that were observed in this family. In both occasions there was a contraction of the CAG tract. Our study demonstrates that SCA1 occurs in the Brazilian population. In addition, our results stress the importance of molecular studies in the confirmation of diagnosis and for pre-symptomatic testing in SCAs.
Subject(s)
Spinocerebellar Degenerations/genetics , Adult , Brazil , Female , Genetic Counseling , Genetic Heterogeneity , Humans , Male , Middle Aged , Mutation , Pedigree , Spinocerebellar Degenerations/bloodABSTRACT
The spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders varying in both clinical manifestations and mode of inheritance. Six different genes causing autosomal dominant SCA are mapped: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, and dentatorubropallidoluysian atrophy (DRPLA). Expansions of an unstable trinucleotide CAG repeat cause three of these disorders: SCA type 1 (SCA1), MJD, and DRPLA. We determine the frequency of the SCA1, DRPLA, and MJD mutations in a large group of unrelated SCA patients with various patterns of inheritance and different ethnic backgrounds. We studied 92 unrelated SCA patients. The frequency of the SCA1 mutation was 3% in the overall patient group and 10% in the non-Portuguese dominantly inherited SCA subgroup. We found that DRPLA mutation in only one Japanese patient, who was previously diagnosed with this disease. We identified the MJD mutation in 41% of the overall patient group, which included 38 autosomal dominant kindreds of Portuguese origin; the frequency of the MJD mutation among the non-Portuguese dominantly inherited cases was 17%. These results suggest that SCA may be occasionally caused by the SCA1 mutation and rarely caused by the DRPLA mutation and that, to date, the MJD mutation seems to be the most common cause of dominantly inherited SCA. Finally, our results suggest that recessively inherited cases of SCA are not caused by the known trinucleotide repeat expansions.
