PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Dominant inheritance”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2003

Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, adult-onset motor neuron disease that arises as a dominantly inherited trait in approximately 10% of ALS cases. Mutations in one gene, cytosolic Cu/Zn superoxide dismutase (SOD1), account for approximately 25% of familial ALS (FALS) cases. We have performed a genetic linkage screen in 16 pedigrees with FALS with no evidence for mutations in the SOD1 gene and have identified novel ALS loci on chromosomes 16 and 20. The analysis of these genes will delineate pathways implicated as determinants of motor-neuron viability and provide insights into possible therapies for ALS.

Adult↗
PubMed1992

Dominantly inherited microcephaly, short stature and normal intelligence.

A large family is reported in which microcephaly and short stature is segregating as a probably autosomal dominantly inherited trait. Some affected members also show a delayed onset of puberty. No other clinical or radiological symptoms are present, and psychomotor development is normal. This short report confirms an earlier description of a similar family by Burton in 1981.

Body Height↗
PubMed1985

Diminished type I collagen synthesis and reduced alpha 1(I) collagen messenger RNA in cultured fibroblasts from patients with dominantly inherited (type I) osteogenesis imperfecta.

Type I osteogenesis imperfecta (OI) is characterized clinically by a moderate fracture frequency with minimal bone deformity and dominant inheritance. Previous studies of the collagenous proteins synthesized by dermal fibroblasts obtained from unrelated patients with this form of OI suggested that the biochemical basis of the disease was reduced production of type I collagen. This study was designed to determine if this biochemical finding segregated with the disease within an individual family. Dermal fibroblast strains were established from three generations of a family having the typical features of type I OI. Analysis of the collagenous proteins made in culture revealed an elevated alpha 1(III) to alpha 1(I) collagen type ratio and an elevated alpha 1(I) to alpha 2(I) collagen chain ratio. The procollagen that accumulated in the medium reflected these ratios to the same degree. Total collagen synthesis was significantly reduced in affected family members. Therefore, the most striking abnormality in affected members was a 50-75% reduction of type I collagen production. Furthermore, the ratio of the alpha 1(I)/alpha 2(I) collagen messenger RNA (mRNA), measured by dot hybridization, was one-half of the value of uninvolved family members and unrelated controls. Since the reduction in the production of type I collagen and the altered alpha 1(I)/alpha 2(I) mRNA ratio clearly segregated with affected individuals within this family, these biochemical measurements may be a useful genetic marker for type I OI.

Adult↗
PubMed2001

Dominantly inherited myopathy with novel tubular aggregates containing 1-21 tubulofilamentous structures.

Tubular aggregates (TAs) in skeletal muscle fibers have been observed as a nonspecific finding in a number of different conditions such as periodic paralysis, myotonic disorders, hyperaldosteronism, chronic use of drugs, and alcoholism. However, TAs were also found more specifically in well-defined muscle disorders, e.g., exercise-induced cramps, myasthenic syndromes, and even in dominantly or recessively inherited familial myopathies. We report on a presumably dominantly inherited familial myopathy with late onset characterized morphologically by the presence of three types of TAs in type II muscle fibers identified in three affected members of one family (a 86-year-old man and his two sons). The first, novel type was characterized by tubules, 30-200 nm in thickness which included 1-21 tubulofilamentous structures 14-18 nm in diameter. The second type of TAs corresponded to previously well-described tubules and were derived from terminal cisternae, which were rather irregularly arranged or widened, and filled with material of medium electron density. The third type of TAs were occasional, hexagonally arranged TAs of the usual type [type Ib and Ic]. Rare annulate lamellae were also seen. Our findings support the evidence of tubular aggregates as the major finding in certain dominantly inherited myopathies. Tubules of the first type, to the best of our knowledge, have not been recorded in any other myopathy. It is therefore suggested that these tubules characterize a novel type of a benign, slowly progressive myopathy with late onset, muscle pain, cramps, and stiffness.

Adult↗
PubMed1975

Dominantly inherited osteogenesis imperfecta in man: an examination of collagen biosynthesis.

We have examined control subjects and patients in an effor to discover a metabolic basis for dominantly inherited osterogenesis imperfecta (OI). Studies were carried out in vitro with cultured skin fibroblasts obtained from OI patients, and in vivo on peptide-bound hydroxyproline excretion in urine. Urinary hydroxyproline excretion (milligrams/24 hr) adjusted for age is essentially normal in OI patients, although the mean excretion rate is below average. The latter finding is presumably a reflection of the smaller body mass of OI patients. The OI skin fibroblasts, matched for age of donor, site of biopsy, phase of growth, and generation number in culture, incorporated L-proline into hot trichloroacetic acid (TCA)-soluble protein (collagen) at normal rates. The rate of conversion of proline to hydroxyproline in the nascent polypeptides is also normal in OI. Incorporation of L-lysine was also normal in OI. These findings indicate that peptide synthesis of collagen is not impaired in OI. Rates of galactose incorporation into collagen and the extractability of collagen into normal saline or 0.2 M citric acid were all normal both in OI cells and in the culture medium recovered from the monolayer. These findings, in combination with the urinary data on hydroxyproline excretion in vivo reveal that cross-linking and export of collagen in OI is essentially normal. The elution profile after ion exchange chromatography of fibroblast collagen on carboxymethyl (CM)--Sephadex was also examined. The normal 2/1 ratio of peak 1 (largely alpha 1(1) chains) to peak 2 ) largely alpha 2 chains) was found in OI fibroblast extracts, which implies that synthesis and initial aggregation of the two types of polypeptide to yield (alpha1(1))-2 alpha 2 collagen composition is not abnormal in OI. Despite the negative biochemical findings, a consistent defect in the morphology of OI cells was identified in the log phase and the confluent phase of monolayer cultures. The finding is characterized by irregular packing of the aggregated cells and by an irregular tessellated appearance of the individual OI fibroblast. This observation reassures us that the inherited defect is expressed in vitro.

Adolescent↗
PubMed1975

Kniest syndrome with dominant inheritance and mucopolysacchariduria.

A mother and daughter with clinical and radiographic findings typical of the Kniest syndrome are reported. It is apparent that this syndrome is dominantly inherited and that sporadic cases may represent fresh mutations. Abnormally high keratan sulfate excretion was found, indicating that the Kniest syndrome is a mucopolysacchariduria.

Adolescent↗
PubMed1987

Uncombable hair (pili trianguli et canaliculi): evidence for dominant inheritance with complete penetrance based on scanning electron microscopy.

Uncombable or spun-glass hair (pili trianguli et canaliculi) is an uncommon condition in which the hair is "unmanageable" and has a distinct appearance on scanning electron microscopy. The hair is usually grossly abnormal in infancy and childhood, but may become normal later in life. Although dominant inheritance has been observed, most cases have been sporadic. Both recessive and dominant transmission with incomplete penetrance have been suggested as modes of inheritance. We report the occurrence of this condition in a young girl, her brother, and her father. Although the proposita and her brother had characteristically uncombable hair, their father appeared normal and denied any history of hair abnormality. However, the characteristic hair morphology was observed on scanning electron microscopy in all 3 relatives, documenting dominant transmission and complete penetrance of the gene in this family.

Child, Preschool↗
PubMed1987

Brain choline acetyltransferase reduction in dominantly inherited olivopontocerebellar atrophy.

We measured the activity of choline acetyltransferase, the cholinergic marker enzyme, in the brains of 17 patients from five established pedigrees with dominantly inherited olivopontocerebellar atrophy (OPCA). OPCA is a group of cerebellar ataxia disorders in which serious intellectual impairment is not typically considered to be an accompanying feature. Patients from all five pedigrees demonstrated markedly reduced choline acetyltransferase activity in the cerebral cortex, with less severe changes in the hippocampus. Although the magnitude of the cortical choline acetyltransferase deficit is comparable to that seen in the brains of patients with Alzheimer's disease, none of our OPCA patients appeared, on last examination, to have severe global dementia of the Alzheimer type. Determination of the clinical significance of our biochemical data must await the results of studies in which the cognitive status of OPCA individuals has been accurately assessed.

Brain↗
PubMed1983

Rod and cone activity in patients with dominantly inherited retinitis pigmentosa: comparisons between psychophysical and electroretinographic measurements.

Extended electroretinographic (ERG) testing has been carried out in a series of patients with retinitis pigmentosa, dominantly inherited. In 36 of 57 cases only cone b waves were evoked. In 20 of these, psychophysical tests showed only cones mediated vision (Massof class I), while in 16 statis scotopic perimetry demonstrated residual rod function (class II). In the remaining cases, where rod ERGs were seen, the light intensities required to evoke responses were not greatly elevated. A computer model was constructed to relate psychophysical threshold measurements to ERG data. This analysis of the results suggests that in one subgroup of patients the scotopic ERG is smaller than expected from the losses of visual field and that in another the psychophysical elevation of rod visual threshold is greater than expected from ERG measurements.

Adolescent↗
PubMed1993

[Mitochondrial myopathy with autosomal dominant inheritance--report of a family and review of the literature].

We report a family of mitochondrial myopathy which appeared to be interited as an autosomal dominant trait. The proband is a 58-year-old Japanese male, who presented with bilateral ptosis, chronic progressive ophthalmopletia, dysphagia, and atrophy of proximal muscles in the upper extremities. There was no cataract or retinal degeneration. Serum creatine kinase (CK) and lactic acid levels were normal. Cardiac evaluations were normal. Muscle biopsy revealed 7% of ragged red fibers. Cytochrome c oxidase activity in the muscle was decreased to 50% of the control value. PCR analysis of muscle mitochondrial DNA revealed 3 large-scale deletions in the non-D-loop regions, ranging in size from 4.2 kb to 5.2 kb. His father, three siblings, and the two children had symptoms similar to the proband. We have reviewed forty-five individuals from six families, including our family, who had mitochondrial myopathy with autosomal dominant inheritance. Frequent manifestations include chronic progressive ophtalmoplegia (91.2%), ptosis (95.6%), hearing loss (72.7%), dysphagia (60.0%), limb weakness (74.1%), and respiratory muscle weakness (75.0%). Interestingly, there is no individual with retinal degeneration or cardiac involvement. Serum CK and lactic acid levels may be elevated. CT of the head is normal. Muscle biopsy shows ragged red fibers and the frequency of cytochrome c oxidase-negative fibers ranges from 0 to 38%. Multiple large-scale deletions of mitochondrial DNA, ranging in size from 4.2 to 8.3 kb, are found in the muscle, all of which are located in the non-D-loop region of the mitochondrial DNA. The multiplicity of deletions may be one to the characteristic features of this form of mitochondrial myopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Dominantly inherited cleft lip and palate in two families.

Two families with non-syndromic cleft lip and cleft palate are described. The linear pattern of inheritance through several generations is difficult to explain by conventional multifactorial models. The pedigrees strengthen the suggestion that a dominantly inherited mutation exists with a major influence on clefting of the lip and palate alone.

Adult↗
PubMed1981

Dominant inheritance of microcephaly with short stature.

A family is reported in which microcephaly has been observed in at least three generations. The pedigree is most consistent with autosomal dominant inheritance. In addition to microcephaly, affected individuals exhibit significantly short stature, ocular anomalies and simple, protruding ears. Intellectual function is in the normal or borderline range.

Female↗
PubMed2001

A Korean family with a dominantly inherited beta-thalassemia due to Hb Durham-N.C./Brescia.

We describe the molecular and the hematological characteristics of a Korean family with a dominantly inherited beta-thalassemia. Carriers were characterized by moderate anemia, hypochromia, microcytosis, elevated Hb A2 and Hb F levels, and splenomegaly. DNA analysis revealed a CTG (Leu) to CCG (Pro) substitution at codon 114 of the beta-globin gene, that leads to a highly unstable hemoglobin variant, Hb Durham-N.C./Brescia, and this was linked to the beta haplotype V, [+----+-], and framework 2. RNA analysis showed that the proband had comparable levels of mutant and normal beta-mRNA. Translation of the mutant mRNA would give rise to non-functional hyperunstable beta-globin chains, and their degradation would, by placing an additional burden on the proteolytic process of the red blood cell precursors, result in a more severe phenotype.

Adolescent↗
PubMed2004

Dominantly inherited ataxia and dysphonia with dentate calcification: spinocerebellar ataxia type 20.

We describe a pedigree of Anglo-Celtic origin with a phenotypically unique form of dominantly inherited spinocerebellar ataxia (SCA) in 14 personally examined affected members. A remarkable observation is dentate nucleus calcification, producing a low signal on MRI sequences. Unusually for an SCA, dysarthria is typically the initial manifestation. Mild pyramidal signs and hypermetric saccades are noted in some. Its distinguishing clinical features, each present in a majority of affected persons, are palatal tremor, and a form of dysphonia resembling spasmodic dysphonia. Repeat expansion detection failed to identify either CAG/CTG or ATTCT/AGAAT repeat expansions segregating with the disease in this family. The testable SCA mutations have been excluded. On linkage analysis, the locus maps to chromosome 11, which rules out all the remaining mapped SCAs except for SCA5. While locus homogeneity with SCA5 is not formally excluded, we consider it rather unlikely on phenotypic grounds, and propose that this condition may represent an addition to the group of neurogenetic disorders subsumed under the rubric SCA. The International Nomenclature Committee has made a provisional assignment of 'SCA20', although firm designation will have to await a definite molecular distinction from SCA5.

Adult↗
PubMed1988

Familial occurrence of malignant lymphoepithelial lesion of the parotid gland in a Finnish family with dominantly inherited trichoepithelioma.

A rare malignant lymphoepithelial lesion (MLEL) of the parotid gland is described in a mother and daughter within one Finnish family. Several cases of dominantly inherited trichoepithelioma were observed in the same family. This is the third published case of familial MLEL, and the first in whites. The simultaneous occurrence of MLEL with hereditary trichoepithelioma is a new finding and may suggest a common genetic background and/or etiology.

Female↗
PubMed1996

Chorioretinal dysplasia-microcephaly-mental retardation syndrome: another family with autosomal dominant inheritance.

We describe a boy and his father with the chorioretinal dysplasia-microcephaly-mental retardation syndrome (CDMMS). Our report extends the phenotypic spectrum of autosomal dominant CDMMS by describing microphthalmia for the first time in an autosomal dominant family. The boy was also severely mentally retarded in contrast to the usual mild mental retardation in AD-CDMMS. Furthermore he had hypertonia, dysmorphic features and low body weight, which are uncommon in AD-CDMMS. CDMMS is a rare disorder. We traced 18 reports on CDMMS including 10 families, 6 with horizontal transmission and 4 with vertical transmission. There are 8 reports and observations on isolated cases with CDMMS. This might imply genetic heterogeneity with autosomal recessive and autosomal dominant inheritance, with a more severe clinical picture in the former but with quite variable inter- and intrafamilial expression. A review of the literature is given. The existence of autosomal recessive inheritance in families with so-called horizontal transmission is discussed as variable expression, reduced penetrance and germline mosaicism may also explain this condition. Careful (particularly ophthalmologic) examination of first degree relatives is necessary before genetic counseling is given.

Chorioretinitis↗
PubMed1988

Brain acetylcholinesterase activity is markedly reduced in dominantly-inherited olivopontocerebellar atrophy.

The activity was measured of the acetylcholine catabolising enzyme acetylcholinesterase (AChE) in brain after necropsy of seven patients from one established pedigree with dominantly-inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder in which neuropathological changes are assumed to be primarily restricted to cerebellum, lower brain stem and spinal cord. Mean AChE activity was significantly reduced in cerebral (-51% to 65%) and cerebellar (-47%) cortex with a less severe change (-37%) in the hippocampus. The magnitude of the enzyme reduction in cerebral cortex was equal to or greater than that reported in brain of demented Alzheimer's and Parkinson's disease patients having loss of AChE-containing nucleus basalis cholinergic neurons. It is concluded that the data provide additional biochemical evidence suggesting a cerebral cortical cholinergic denervation in OPCA.

Acetylcholinesterase↗