Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Recessive”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 991 records · Page 55Linked to original sources
PubMed2006

Autosomal recessive mutilating sensory neuropathy with spastic paraplegia maps to chromosome 5p15.31-14.1.

Autosomal recessive ulcero-mutilating neuropathy with spastic paraplegia is a very rare disease since only few cases were described up to date. We report in this study a consanguineous Moroccan family with four affected males with this syndrome. The disease onset was in early infancy, with spastic paraplegia and sensory loss leading to mutilating acropathy. Electrophysiological studies revealed a severe axonal sensory neuropathy, magnetic resonance imaging ruled out compression of spinal cord and biological investigations showed decreased levels of Apo B, total cholesterol and triglycerides. A genomewide search was conducted in this family and linkage was found to chromosome 5p. Analysis of recombination events and LOD score calculation map the responsible gene in a 25 cM genetic interval between markers D5S2054 and D5S648. A maximum LOD score value of 3.92 was obtained for all markers located in this candidate interval. This study establishes the presence of a locus for autosomal recessive mutilating sensory neuropathy with spastic paraplegia on chromosome 5p15.31-14.1.

Chromosome Mapping↗
PubMed2006

MORM syndrome (mental retardation, truncal obesity, retinal dystrophy and micropenis), a new autosomal recessive disorder, links to 9q34.

A consanguineous pedigree is described where 14 individuals are affected with a novel autosomal recessive disorder, which causes static moderate mental retardation, truncal obesity, a congenital nonprogressive retinal dystrophy and micropenis in males. We have tentatively named this condition MORM syndrome. It shows similarities to Bardet-Biedl syndrome and Cohen syndrome, but can be distinguished by clinical features; the age of onset and nonprogressive nature of the visual impairment, the lack of characteristic facies, skin or gingival infection, microcephaly, 'mottled retina', polydactyly and small penis without testicular anomalies. Furthermore, linkage to the known Bardet-Biedl (BBS1-8) and Cohen syndrome loci was excluded. Autozygosity mapping identified a single homozygous subtelomeric region shared by all affecteds on chromosome 9q34.3, with a maximum LOD score of 5.64. We believe this to be the first example of the identification of a subtelomeric recessive locus by autozygosity mapping.

Chromosome Mapping↗
PubMed2006

Three different ABCA4 mutations in the same large family with several consanguineous loops affected with autosomal recessive cone-rod dystrophy.

A large multiplex family presumably affected with autosomal recessive cone-rod dystrophy (CRD) was ascertained from Israel. In this family of Christian Arab ancestry with six consanguineous loops, linkage analysis failed to identify homozygosity in all six nuclear families at any of the three arCORD loci hitherto reported. However, homozygosity was found at the CORD3 locus for two nuclear families and the segregation of three distinct haplotypes at this locus in the whole pedigree suggested the alteration of the ABCA4 gene. This hypothesis was confirmed by the identification of three distinct mutations. Subsequently, with regard to the wide spectrum of autosomal recessive retinal dystrophies related to ABCA4 mutations, the natural history of the disease was revisited in all patients. Although the diagnosis of CRD was confirmed in 8/9 patients, the last one, aged of 34, displayed typical signs of Stargardt disease without extension to the peripheral retina. The results of this study emphasize the pitfalls of homozygosity mapping in highly inbred families when the heterozygote carrier frequency is particularly high in the general population.

ATP-Binding Cassette Transporters↗
PubMed2006

Genetic screening for autosomal recessive nonsyndromic mental retardation in an isolated population in Israel.

Nonsyndromic mental retardation (NSMR) is the diagnosis of exclusion in mentally retarded individuals without additional abnormalities. We have recently identified a protein-truncating mutation, G408fsX437, in the gene CC2D1A on chromosome 19p13.12 in nine consanguineous Israeli Arab families with severe autosomal recessive NSMR, and have developed a comprehensive prevention program among the at-risk population in the village. The subjects tested were healthy women who were invited to undergo the genetic screening test as a part of their routine pregnancy monitoring. One hundred and seventeen subjects reported a family history positive for mental retardation. We tested 524 pregnant or preconceptional women and found 47 carriers (approximately 1/11), whose spouses were then recommended to undergo testing. We identified eight carrier couples, who were given genetic counseling and offered prenatal diagnosis. Of all the marriages, 28.6% were consanguineous; 16.5% of the total were between first cousins. The high prevalence of the mutation can be explained both by the founder effect owing to the generally high consanguinity rate among the inhabitants of the village, and also because two families with excessive numbers of mentally retarded offspring were unacceptable as marriage partners by the rest of the families. This is the first example of the establishment of a large-scale genetic screening program for autosomal recessive NSMR, which was made possible owing to the high frequency of the specific causative mutation in this isolated population.

DNA-Binding Proteins↗
PubMed2006

Pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity.

Pseudoxanthoma elasticum (PXE) is caused by mutations in the ABCC6 gene. Historically, PXE has been suggested to be inherited either in an autosomal dominant or autosomal recessive manner. To determine the exact mode of inheritance of PXE and to address the question of phenotypic expression in mutation carriers, we identified seven pedigrees with affected individuals in two different generations and sequenced the entire coding region of ABCC6 in affected individuals, presumed carriers with a limited phenotype and unaffected family members. Two allelic mutations were identified in each individual with unambiguous diagnosis of PXE, as well as in those with only minimal clinical signs suggestive of PXE but with positive skin biopsy. Missense mutations were frequently detected in the latter cases. In conclusion, PXE is inherited in an autosomal recessive manner and presence of disease in two generations is due to pseudodominance.

DNA Mutational Analysis↗
PubMed2006

Homozygous missense mutation in fibulin-5 in an Iranian autosomal recessive cutis laxa pedigree and associated haplotype.

Cutis laxa is a rare group of inherited and acquired disorders characterized by loose and redundant skin with reduced elasticity. Mutations in the elastin coding gene have been shown to cause autosomal dominant cutis laxa in three families. A homozygous mutation in the fibulin-5 coding gene was discovered in a Turkish pedigree showing recessive inheritance, and a different mutation in this gene was found in the heterozygous state in a sporadic case of the disease. Here, we report the third case of a mutation in the fibulin-5 coding gene in a recessive Iranian cutis laxa pedigree. The mutation is the same as previously reported in the Turkish pedigree, further confirming that it is causative of disease. A haplotype consisting of seven intragenic sequence variations common to both pedigrees is described for the mutation-carrying fibulin-5 allele.

Adolescent↗
PubMed1998

Frameshift mutations in the type VII collagen gene (COL7A1) in five Mexican cousins with recessive dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the type VII collagen gene (COL7A1). In this study, we assessed the molecular basis of recessive DEB in five affected individuals from two Mexican families. Both fathers of the affected children were first cousins. Genomic DNA was extracted from peripheral blood samples and assessed for COL7A1 mutations by polymerase chain reaction (PCR) amplification, heteroduplex analysis and direct automated sequencing of PCR products displaying heteroduplex bandshifts. In one family, we identified a homozygous 1 bp insertion of a G nucleotide in exon 19 of COL7A1, designated 2470insG, in three affected sisters. This mutation causes a frameshift and a premature termination codon on both alleles 178 bp downstream from the insertion; both parents were shown to be heterozygous carriers of this mutation. In the second family, the father of the other two affected children was also found to be a heterozygous carrier of this frameshift mutation. In addition, his unrelated partner was shown to be a heterozygous carrier of a different COL7A1 frameshift mutation, an insertion of a T nucleotide in exon 32, designated 3948insT. This mutation also results in a premature termination codon, 126 bp downstream from the insertion. Both affected children were compound heterozygotes for the 2470insG/3948insT mutations in COL7A1. Overall, these molecular findings offer a genetic explanation for the skin fragility in these related Mexican patients with recessive DEB. Immediate benefits from elucidation of the mutations include assessment of carrier status in other members of the family and the feasibility of DNA-based prenatal testing in subsequent pregnancies.

Adolescent↗
PubMed2002

Different phenotypes in recessive dystrophic epidermolysis bullosa patients sharing the same mutation in compound heterozygosity with two novel mutations in the type VII collagen gene.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a bullous skin disease caused by mutations in the type VII collagen gene (COL7A1). OBJECTIVE: To elucidate the mutations shown by two patients with DEB and understand the clinical phenotypes that they displayed. METHODS: We have characterized two patients, one affected by the severe recessive Hallopeau-Siemens variant of DEB (HS-RDEB) and the other by a milder recessive DEB form. RESULTS: In both patients we identified the R2063W missense mutation. The second mutation, in the HS-RDEB patient, was a novel 344insG, leading to a premature termination codon of translation (PTC) in exon 3, while, in the other patient, it was a novel 4965C-->T transition, which creates a new donor splice site in exon 53. The effect of this anomalous splice site leads to the maturation of a 17-nucleotides-deleted mRNA containing a PTC. In addition to this aberrant transcript, a certain amount of full-length mRNA is also generated from the mutated pre-mRNA through splicing at the canonical site. CONCLUSIONS: In these patients therefore the severity of the phenotype depends on the second mutation. In the patient with the 344insG mutation, leading to a PTC, type VII collagen (COLVII) molecules are exclusively composed of chains containing the R2063W substitution; as a consequence, all anchoring fibrils (AF) are abnormal and the phenotype is severe. In the other patient, the 4965C-->T splicing mutation allows the synthesis of a certain quantity of normal chains and the consequent assembly of partially functional COLVII molecules and AF, thus explaining the mild phenotype.

Adolescent↗
PubMed2000

Coinheritance of two alpha-spectrin gene defects in a recessive spherocytosis family.

We studied a recessive hereditary spherocytosis (HS) family from Norway in which all four children had haemolytic spherocytosis while spectrin (Sp) deficiency was detected in the proband. Molecular analysis demonstrated that all affected children had inherited the low expression alpha-Sp allele LEPRA (Low Expressed PRAgue) from the father. Haplotyping with a polymorphic dinucleotide repeat for the alpha-Sp gene (alphaVNTR) located in the 3' untranslated region of mRNA showed that all recessive children had inherited the same maternal alpha-spectrin allele. The paternal Sp-alphaLEPRA allele was found in cis of the polymorphic alpha-Sp Bughill allele (alphaBH) characterized by the A970D point mutation in the Sp alpha-chain. This mutation was identified on two-dimensional electrophoresis of Sp tryptic digests as an acidic shift of the alphaII tryptic domains (spots alphaIIa). Analyses of the relative expression of the paternal alpha-Sp Bughill polymorphism in the proband showed that the product of the maternal alpha-Sp gene is almost completely absent from the mature erythrocyte membrane. Comparative analysis between alphaVNTR PCR-amplified from genomic DNA and from cDNA showed that the maternal low expression alpha-Sp allele is associated with a decreased amount of mRNA. Results from molecular and biochemical studies showed that all the affected children of this family are compound heterozygous for two different low expression alpha-Sp alleles: an uncharacterized defective alpha-Sp allele on the maternal side and an alphaLEPRA allele tagged by the alphaIIa polymorphism on the paternal side.

Anemia↗
PubMed1998

recessive spotting: a linked locus that interacts with W/Kit but is not allelic.

BACKGROUND: The murine coat-colour mutation recessive spotting (rs) maps very closely to the W/Kit locus, encoding the proto-oncoprotein Kit, the protein tyrosine kinase receptor for stem cell factor. Kit is important in the development of melanocytes, germ cells, interstitial cells of Cajal (ICC) and haemopoietic lineages, including mast cells. rs has never been genetically separated from Kit, and interacts with Kit mutations, suggesting that it is a recessive allele of Kit. Here we have tested this possibility. We have shown previously that diploid rs/rs melanocytes proliferated more slowly than did +/+ melanocytes, as did an immortal line of rs/rs melanocytes, melan-rs. RESULTS: The Kit mRNA level in rs/rs melanocytes was indistinguishable from that of other melanocyte lines. The Kit cDNA sequence from rs/rs melanocytes and the kinase activity of Kit in rs/rs mast cells appeared to be normal. No deficiency of mast cells or ICC was observed in rs/rs mice. Moreover, following the overexpression of a normal Kit cDNA, proliferation of rs/rs melanocytes was retarded further, but that of +/+ melanocytes was increased, indicating an intracellular interaction between rs and Kit. Of other closely linked tyrosine kinase genes, melanocytes and melanoblasts did not express mRNA for Pdgfra, Flk-1 or Txk, but both expressed Tec, encoding a nonreceptor kinase that interacts with Kit. CONCLUSIONS: rs is not a mutation in Kit, although we have confirmed that rs interacts with Kit. It seems unlikely that rs affects Pdgfra, Flk-1 or Txk, but Tec remains a candidate for rs.

Alleles↗
PubMed2002

Papilla base incision: a new approach to recession-free healing of the interdental papilla after endodontic surgery.

AIM: The purpose of the present study was to describe and evaluate a new incision technique: the papilla base incision. METHODOLOGY: Twenty healthy patients referred for surgical treatment of persisting apical periodontitis, who were free of periodontal disease and had intact interdental papillae were included in the study. The preoperative papilla height was recorded by measuring the distance between the contact point and the most coronal point of the papilla. The papilla base flap, consisting of the papilla base incision and two releasing incisions, was used to expose the bone. The papilla base incision consisted of a shallow first incision at the base of the papilla and a second incision directed to the crestal bone, creating a split thickness flap in the area of the papilla base. Further apically a full thickness flap was raised. Following standard root-end resection and filling, flap closure was achieved with microsurgical sutures. The papilla base incision was sutured with 2-3 interrupted sutures, which were removed 3-5 days after the surgery. The experimental sites were evaluated at the conclusion of the surgery, at suture removal and after 1 month, and compared to the preoperative findings. The healing pattern, complications and postoperative recession were recorded. The experimental sites were observed with a x 3 magnification and graded as to whether a visible scar resulting from the incision could be detected. Twenty experimental sites were analysed. RESULTS: Complete closure of the wound was achieved in all cases after surgery. Except for four patients with delayed healing at suture removal, all other patients displayed rapid healing. No noticeable space was created beneath the contact point area. The change in distance between the reference point and the most coronal point of the papilla comparing the preoperative and the one-month postoperative situation was 0.05 +/- 0.39 mm. The probing depth remained within normal limits. One month postoperatively, observation of the incision demonstrated: four sites with a visible incision line (grade 1), in seven sites the incision defect could be partially detected (grade 2) and nine incisions could not be detected (grade 3). CONCLUSIONS: In patients with healthy marginal periodontal conditions the papilla base incision allows rapid and predictable recession-free healing following marginal surgical exposure of the soft tissues. One month postoperatively the majority of the incisions were completely or partially invisible. Long-term healing will be studied.

Adult↗
PubMed2002

A natural recessive resistance gene against potato virus Y in pepper corresponds to the eukaryotic initiation factor 4E (eIF4E).

We show here that the pvr2 locus in pepper, conferring recessive resistance against strains of potato virus Y (PVY), corresponds to a eukaryotic initiation factor 4E (eIF4E) gene. RFLP analysis on the PVY-susceptible and resistant pepper cultivars, using an eIF4E cDNA from tobacco as probe, revealed perfect map co-segregation between a polymorphism in the eIF4E gene and the pvr2 alleles, pvr2(1) (resistant to PVY-0) and pvr2(2) (resistant to PVY-0 and 1). The cloned pepper eIF4E cDNA encoded a 228 amino acid polypeptide with 70-86% nucleotide sequence identity with other plant eIF4Es. The sequences of eIF4E protein from two PVY-susceptible cultivars were identical and differed from the eIF4E sequences of the two PVY-resistant cultivars Yolo Y (YY) (pvr2(1)) and FloridaVR2 (F) (pvr2(2)) at two amino acids, a mutation common to both resistant genotypes and a second mutation specific to each. Complementation experiments were used to show that the eIF4E gene corresponds to pvr2. Thus, potato virus X-mediated transient expression of eIF4E from susceptible cultivar Yolo Wonder (YW) in the resistant genotype YY resulted in loss of resistance to subsequent PVY-0 inoculation and transient expression of eIF4E from YY (resistant to PVY-0; susceptible to PVY-1) rendered genotype F susceptible to PVY-1. Several lines of evidence indicate that interaction between the potyvirus genome-linked protein (VPg) and eIF4E are important for virus infectivity, suggesting that the recessive resistance could be due to incompatibility between the VPg and eIF4E in the resistant genotype.

Alleles↗
PubMed2001

Autosomal recessive deficiencies of coagulation factors.

Deficiencies of coagulation factors that cause a bleeding disorder, other than factor VIII and factor IX, are inherited as autosomal recessive traits and are generally rare, with prevalence in the general population varying between 1 in 500 000 and 1 in 2 000 000. In the last few years, the number of patients with recessively transmitted coagulation deficiencies has increased in European countries with a high rate of immigration of Islamic populations where consanguineous marriages are frequent. As a consequence of the relative rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects and the actual management of bleeding episodes are not as well established as for hemophilia A and B. This article reviews these disorders, in terms of clinical manifestations and characterization of the molecular defects. The general principles of management are also discussed.

Blood Coagulation Disorders, Inherited↗
PubMed2000

Coexistence of dominant and recessive familial amyotrophic lateral sclerosis with the D90A Cu,Zn superoxide dismutase mutation within the same country.

The Cu,Zn superoxide dismutase (Cu,Zn SOD) mutations described in amyotrophic lateral sclerosis (ALS) have, for the most part, a dominant influence. However, while a few cases with a heterozygous D90A mutation have been described in different countries, D90A has been recently proven to be recessively inherited with a common founder effect in Scandinavia. We screened French ALS families for Cu,Zn SOD mutations. The presence of the D90A allele was found in two index-cases, and their families were subsequently studied. In the first family the ALS patients were homozygotes for D90A, while in the second, all ALS patients were heterozygotes. In both families the disease was found to initially involve the lower limbs with slower progression than in sporadic cases, and frequent atypical signs such as paresthesia and urgency of micturition. We determined the D90A allele frequency in controls (n = 200) and sporadic ALS patients (n = 408). No D90A allele was found. This is the first report of coexistence of dominant and recessive families with the D90A Cu,Zn SOD mutation within the same country.

Adult↗
PubMed2003

Functional analysis of connexin-26 mutants associated with hereditary recessive deafness.

The physiological importance of connexin-26 (Cx26) gap junctions in regulating auditory function is indicated by the finding that autosomal recessive DFNB1 deafness is associated with mutations of the Cx26 gene. To investigate the pathogenic role of Cx26 mutation in recessive hearing loss, four putative DFNB1 Cx26 mutants (V84L, V95M, R127H, and R143W) were stably expressed in N2A cells, a communication-deficient cell line. In N2A cells expressing (R127H) Cx26 gap junctions, macroscopic junctional conductance and ability of transferring neurobiotin between transfected cells were greatly reduced. Despite the formation of defective junctional channels, immunoreactivity of (R127H) Cx26 was mainly localized in the cell membrane and prominent in the region of cell-cell contact. Mutant (V84L), (V95M), or (R143W) Cx26 protein formed gap junctions with a junctional conductance similar to that of wild-type Cx26 junctional channels. (V84L), (V95M), or (R143W) Cx26 gap junctions also permitted neurobiotin transfer between pairs of transfected N2A cells. The present study suggests that (R127H) mutation associated with hereditary sensorineural deafness results in the formation of defective Cx26 gap junctions, which may lead to the malfunction of cochlear gap junctions and hearing loss. Further studies are required to determine the exact mechanism by which mutant (V84L), (V95M), and (R143W) Cx26 proteins, which are capable of forming functional homotypic junctional channels in N2A cells, cause the cochlear dysfunction and sensorineural deafness.

Amino Acid Substitution↗
PubMed2002

Multiorgan mRNA misexpression in murine autosomal recessive polycystic kidney disease.

BACKGROUND: BALB/c mice homozygous for the cpk mutation develop a form of polycystic kidney disease (PKD) with multiorgan pathology similar to human autosomal recessive PKD. Messenger RNA expression in multiple affected organs was analyzed to determine if common gene cascades were misexpressed in the cystic kidney and extrarenal sites of disease. In cystic kidneys, misexpressed mRNAs were found in one of four general groups: proliferation/cell growth, apoptosis, differentiation or extracellular matrix. METHODS: RNA was isolated from kidney, liver and pancreas of cystic and normal BALB/c-cpk mice. Using Northern blot hybridization and ribonuclease protection assays (RPA), the expression of several genes thought to be associated with PKD, namely c-myc, epidermal growth factor receptor (EGF-R) and PKD-1, were evaluated. RPAs were used to assess mRNA expression of cyclins and members of the bax/bcl-2 family. In addition, kidney, liver and pancreas were immunostained for c-Myc and PCNA. RESULTS: Cystic kidney, liver and pancreas all exhibited similar patterns of mRNA misexpression of c-myc, EGF-R and PKD-1. In addition, a number of cell proliferation and apoptosis-related mRNAs also were elevated in cystic kidney and pancreas. Renal epithelial cells expressing proliferation-associated proteins [c-Myc and proliferating cell nuclear antigen (PCNA)] were nearly absent in normal kidney; however, cells of cystic and non-cystic renal tubules plus liver and pancreatic cyst exhibited an increased number of nuclei labeled with antibodies to these proteins. CONCLUSIONS: These data suggest that similar pathologic mechanisms (including the expression of c-myc, EGF-R, PKD-1, cyclin, and bax/bcl-2 family mRNAs) may be responsible for the development of cystic changes in kidney, liver and pancreas in murine autosomal recessive PKD. Treatments targeting these similarly misexpressed mRNAs may be efficacious in ameliorating the cystic pathology in the kidney as well as the other affected organs in ARPKD.

Animals↗
PubMed2004

Autosomal recessive renal proximal tubulopathy and hypercalciuria: a new syndrome.

BACKGROUND: The best described primary inherited proximal tubulopathies include X-linked hypercalciuric nephrolithiasis (XLHN), caused by a mutation in the chloride channel gene CLCN5, and classic Fanconi's syndrome, the genetic basis of which is unknown. The aim of this study is to examine the clinical, biochemical, and genetic characteristics of a highly consanguineous Druze family with autosomal recessive proximal tubulopathy and hypercalciuria (ARPTH), a syndrome not reported previously. METHODS: Three children (2 girls, 1 boy) of the family referred for evaluation of renal glycosuria and hypercalciuria and 10 of their close relatives were evaluated clinically and biochemically. All study participants underwent genetic analysis to exclude involvement of the CLCN5 gene. RESULTS: Evaluation of the 3 affected children showed glycosuria, generalized aminoaciduria, hypouricemia, uricosuria, low molecular weight (LMW) proteinuria, and hypercalciuria in all 3 children and phosphaturia in 2 children. They had no metabolic acidosis or renal insufficiency. One affected girl had nephrocalcinosis. Two children had a history of growth retardation and radiological findings of metabolic bone disease. Parathyroid hormone and 1,25-dihydroxyvitamin D [1,25(OH)2Vit D] blood levels in affected children were normal. Unaffected family members examined had no renal tubular defects or LMW proteinuria. Genetic linkage analysis excluded cosegregation of the ARPTH phenotype with the CLCN5 locus. CONCLUSION: ARPTH is a new syndrome characterized by nonacidotic proximal tubulopathy, hypercalciuria, metabolic bone disease, and growth retardation. It can be distinguished from XLHN by its autosomal recessive mode of inheritance and normal serum levels of calciotropic hormones, as well as the absence of LMW proteinuria in obligate carriers. The gene mutated in ARPTH remains to be identified.

Bone Diseases, Metabolic↗
PubMed1992

Autosomal recessive microcephaly with severe psychomotor retardation.

Autosomal recessive microcephaly has long been recognized in association with normal early motor development and mild to severe mental retardation. We report three sibling pairs with microcephaly and severe neurological impairment. These cases and other sibling pairs reported in the literature illustrate that microcephaly with spasticity and severe mental retardation may also have autosomal recessive inheritance. Furthermore this severely affected group of patients forms a significant proportion of cases of genetic microcephaly. We looked for specific morphological features to identify these forms of genetic microcephaly for genetic counselling, but failed to find characteristic abnormalities among our group of patients.

Adolescent↗