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M Litt

Publications and source records attributed to M Litt.

At least 19 recordsLinked to original sources
PubMed2005

Fifty-four new gene-based canine microsatellite markers.

Fifty-four new markers were developed to fill in gaps in the current map of canine microsatellites and to complement existing markers that may not be sufficiently informative in highly inbred canine pedigrees. Canine genes contained on the radiation hybrid map were used to obtain the sequence of the human homolog. A BLAST search versus the canine whole genome shotgun (wgs) sequence resource was used to obtain the sequence of the canine genomic contigs containing the homolog of the corresponding human gene. Canine sequences that contained microsatellites and mapped back to the correct location in the human genome were used to design primers for amplification of the microsatellites from canine genomic DNA. Heterozygosities of the markers were tested by genotyping grandparental DNAs obtained from the Nestle Purina Reference family DNA distribution center plus DNAs from unrelated Bouviers and Irish wolfhounds. Canine map positions of markers on the July 2004 freeze of the canine genome assembly were determined by in silico PCR or BLAST.

Animals↗
PubMed2001

Novel lamin A/C mutations in two families with dilated cardiomyopathy and conduction system disease.

BACKGROUND: The LMNA gene, one of 6 autosomal disease genes implicated in familial dilated cardiomyopathy, encodes lamins A and C, alternatively spliced nuclear envelope proteins. Mutations in lamin A/C cause 4 diseases: Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy type 1B, Dunnigan-type familial partial lipodystrophy, and dilated cardiomyopathy. METHODS AND RESULTS: Two 4-generation white families with autosomal dominant familial dilated cardiomyopathy and conduction system disease were found to have novel mutations in the rod segment of lamin A/C. In family A a missense mutation (nucleotide G607A, amino acid E203K) was identified in 14 adult subjects; disease was manifest as progressive conduction disease in the fourth and fifth decades. Death was caused by heart failure. In family B a nonsense mutation (nucleotide C673T, amino acid R225X) was identified in 10 adult subjects; disease was also manifest as progressive conduction disease but with earlier onset (third and fourth decades), ventricular dysrhythmias, left ventricular enlargement, and systolic dysfunction. Death was caused by heart failure and sudden cardiac death. Skeletal muscle disease was not observed in either family. CONCLUSIONS: Novel rod segment mutations in lamin A/C cause variable conduction system disease and dilated cardiomyopathy without skeletal myopathy.

Adult↗
PubMed2000

Paroxysmal kinesigenic dyskinesia and infantile convulsions: clinical and linkage studies.

OBJECTIVE: To clinically characterize affected individuals in families with paroxysmal kinesigenic dyskinesia (PKD), examine the association with infantile convulsions, and confirm linkage to a pericentromeric chromosome 16 locus. BACKGROUND: PKD is characterized by frequent, recurrent attacks of involuntary movement or posturing in response to sudden movement, stress, or excitement. Recently, an autosomal dominant PKD locus on chromosome 16 was identified. METHODS: The authors studied 11 previously unreported families of diverse ethnic background with PKD with or without infantile convulsions and performed linkage analysis with markers spanning the chromosome 16 locus. Detailed clinical questionnaires and interviews were conducted with affected and unaffected family members. RESULTS: Clinical characterization and sampling of 95 individuals in 11 families revealed 44 individuals with paroxysmal dyskinesia, infantile convulsions, or both. Infantile convulsions were surprisingly common, occurring in 9 of 11 families. In only two individuals did generalized seizures occur in later childhood or adulthood. The authors defined a 26-cM region using linkage data in 11 families (maximum lod score 6.63 at theta = 0). Affected individuals in one family showed no evidence for a shared haplotype in this region, implying locus heterogeneity. CONCLUSIONS: Identification and characterization of the PKD/infantile convulsions gene will provide new insight into the pathophysiology of this disorder, which spans the phenotypic spectrum between epilepsy and movement disorder.

Adolescent↗
PubMed2000

Autosomal-dominant congenital cataract associated with a deletion mutation in the human beaded filament protein gene BFSP2.

Congenital cataracts are a common major abnormality of the eye that frequently cause blindness in infants. At least one-third of all cases are familial; autosomal-dominant congenital cataract appears to be the most-common familial form in the Western world. Elsewhere, in family ADCC-3, we mapped an autosomal-dominant cataract gene to chromosome 3q21-q22, near the gene that encodes a lens-specific beaded filament protein gene, BFSP2. By sequencing the coding regions of BFSP2, we found that a deletion mutation, DeltaE233, is associated with cataracts in this family. This is the first report of an inherited cataract that is caused by a mutation in a cytoskeletal protein.

Amino Acid Sequence↗
PubMed2000

Numerical model and experimental validation of microcarrier motion in a rotating bioreactor.

The equations of motion for microcarriers in a rotating bioreactor have been formulated and trajectories obtained using numerical techniques. An imaging system was built to validate the results by direct observation of microcarrier trajectories in the rotating frame of reference. The microcarrier motion observed by this imaging system was in excellent agreement with the numerical predictions of that motion. In the rotating frame of reference, microcarriers with density greater than the surrounding fluid medium followed a circular motion relative to the culture medium combined with a persistent migration and eventual collision with the outer wall of the reactor. However, for microcarrier density less the fluid medium, their circular motion migrated toward the central region of the reactor. When multiple microcarrier beads that are lighter than water are inserted into the reactor, the centrally directed migration results in the formation of clusters that are stabilized by tissue bridges formed by osteoblasts seeded onto the microcarriers. This system offers unique opportunities to monitor tissue synthesis on microcarriers using real-time optical techniques and to optimize the bioreactor operating conditions for exploiting this technology to study early bone tissue synthesis in vitro.

Bioreactors↗
PubMed2000

A new locus for autosomal dominant congenital cataracts maps to chromosome 3.

PURPOSE: To map a gene for cataracts in a family with congenital nuclear and sutural cataracts and to examine candidate genes in the linked region. METHODS: A large family with autosomal dominant congenital nuclear and sutural cataracts was identified and characterized. A genome-wide screen was conducted with a set of markers spaced at 10- to 15-cM intervals, and linkage was assessed using standard LOD score analysis. RESULT: Fifteen (15) affected individuals were identified. This form of congenital cataracts maps to a 12-cM region on chromosome 3q21.2-q22.3 between markers D3S3674 and D3S3612, with a maximum multipoint LOD score of 6.94 at D3S1273. The crystallin gene, CRYGS, was excluded as a candidate gene for this locus. CONCLUSIONS: There are now more than 12 different genetic loci that cause congenital cataracts. The most recent locus to be identified is on chromosome 3q21.2-q22.3, in a family with congenital nuclear and sutural cataracts.

Adult↗
PubMed1999

A novel nonsense mutation in CACNA1A causes episodic ataxia and hemiplegia.

OBJECTIVE: To identify the disease-causing mutation and to characterize penetrance and phenotypic variability in a large pedigree with episodic ataxia type 2 (EA-2) previously linked to chromosome 19. BACKGROUND: Mutations in the CACNA1A gene on chromosome 19 encoding a calcium channel subunit cause EA-2, which is characterized by recurrent attacks of imbalance with interictal eye movement abnormalities. METHODS: The authors used single-strand conformation polymorphism (SSCP) analysis to screen for point mutations, and direct sequencing to identify mutations in CACNA1A. Allele-specific oligonucleotides were designed to detect the presence of the diseased allele in members of their pedigree as well as in normal control subjects. RESULTS: Reassessment of members of the pedigree revealed two notable clinical features. Diffuse weakness during attacks of ataxia was a prominent complaint. Two affected individuals had had episodic hemiplegia, one with typical migraine headaches. SSCP analysis revealed aberrant bands in exon 29 in affected members but not in normal control subjects. Direct sequencing of exon 29 identified a C-to-T change at position 4914 of the coding sequence of CACNA1A, predicting an early stop code at codon 1547. Two asymptomatic mutation carriers demonstrated the incomplete penetrance of this mutation. CONCLUSIONS: A nonsense mutation in CACNA1A causes episodic ataxia and complaint of weakness, and may be associated with hemiplegia.

Adolescent↗
PubMed1999

Control of transmission of vancomycin-resistant Enterococcus faecium in a long-term-care facility.

OBJECTIVES: To describe the investigation and control of transmission of vancomycin-resistant enterococci (VRE) in a residential long-term-care (LTC) setting. OUTBREAK INVESTIGATION: A strain of vancomycin-resistant Enterococcus faecium not previously isolated in Ontario colonized five residents of a 254-bed LTC facility in Toronto. The index case was identified when VRE was isolated from a urine culture taken after admission to a local hospital. Screening of rectal swabs from all 235 residents identified four others who were colonized with the same strain of E faecium. CONTROL MEASURES: Colonized residents were cohorted. VRE precautions were established as follows: gown and gloves for resident contact, restriction of contact between colonized and noncolonized residents, no sharing of personal equipment, and daily double-cleaning of residents' rooms and wheelchairs. OUTCOME: Two colonized residents died of causes unrelated to VRE. Although bacitracin therapy (75,000 units four times a day x 14 days) failed to eradicate carriage in two of three surviving residents, both cleared their carriage within 7 weeks. Repeat rectal swabs from 224 residents (91%) 2 months after isolation precautions were discontinued and from 125 residents (51%) 9 months later identified no new cases. Total cost of investigation and control was $12,061 (Canadian). CONCLUSION: VRE may be transmitted in LTC facilities, and colonized LTC residents could become important VRE reservoirs. Control of VRE transmission in LTC facilities can be achieved even with limited resources.

Aged↗
PubMed1999

Gene structure and chromosome mapping of the human small-conductance calcium-activated potassium channel SK1 gene (KCNN1).

Small-conductance, calcium-activated potassium channels contribute to the afterhyperpolarization in central neurons and other cell types. Because these channels regulate neuronal excitability, defects in their genes could cause excitability disorders. The human cDNA encoding one such channel, SK1 (KCNN1), was recently cloned. Here we describe the gene structure of KCNN1 and its localization by radiation hybrid mapping to chromosome 19p13.1.

Animals↗
PubMed1998

Further localization of a gene for paroxysmal dystonic choreoathetosis to a 5-cM region on chromosome 2q34.

Paroxysmal dystonic choreoathetosis (PDC) is a rare neurological disorder characterized by episodes of involuntary movement, involving the extremities and face, which may occur spontaneously or be precipitated by caffeine, alcohol, anxiety, and fatigue. PDC is transmitted as an autosomal dominant trait with incomplete penetrance. A gene implicated in this paroxysmal disorder has been mapped to a 10-15 cM region on chromosome 2q31-36 in two families. We describe a third family with PDC. Two-point linkage analyses with markers linked to the candidate PDC locus were performed. A maximum two-point LOD score of 4.20 at a recombination fraction of zero was obtained for marker D2S120, confirming linkage to the distal portion of chromosome 2q. The anion exchanger gene, SLC2C, maps to this region, but the family was poorly informative for polymorphic markers within and flanking this candidate gene. Haplotype analysis revealed a critical recombination event that confines the PDC gene to a 5-cM region bounded by the markers D2S164 and D2S377. We compared the haplotype in our family with that in another chromosome 2-linked PDC family, but did not detect a region of shared genotypes. However, identifying a third family whose disease maps to the same region and narrowing the critical region will facilitate identification of the 2q-linked PDC gene.

Adult↗
PubMed1998

Confirmation of linkage of Clouston syndrome (hidrotic ectodermal dysplasia) to 13q11-q12.1 with evidence for multiple independent mutations.

Clouston syndrome (hidrotic ectodermal dysplasia) is an autosomal dominant disorder characterized by the triad of nail dystrophy, alopecia, and palmoplantar hyperkeratosis. Recently, linkage of a Clouston syndrome locus to chromosome 13q11-q12.1 was reported in eight families of French-Canadian descent. We have confirmed linkage to this region in four additional families: two of French-Canadian descent, one of Scottish-Irish descent, and one French family. Multipoint linkage analysis gave a lod score of 5.09 at marker D13S175. The two families of French-Canadian descent share haplotypes with those reported by Kibar et al (1996), indicating a common founder. The French and Scottish-Irish families do not demonstrate the common haplotype, indicating that the mutations in these populations are most likely of different origin.

Chromosomes, Human, Pair 13↗
PubMed1998

Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA.

Congenital cataracts are a common major abnormality of the eye that frequently cause blindness in infants. At least a third of all cases are familial; autosomal dominant congenital cataract (ADCC) appears to be the most common familial form in the Western world. We have mapped an ADCC gene in family ADCC-2 to chromosome 21q22.3 near the alpha-crystallin gene CRYAA. By sequencing the coding regions of CRYAA, we found that a missense mutation, R116C, is associated with ADCC in this family.

Amino Acid Sequence↗
PubMed1997

Invasive infections due to a fish pathogen, Streptococcus iniae. S. iniae Study Group.

BACKGROUND: Streptococcus iniae is a pathogen in fish, capable of causing invasive disease and outbreaks in aquaculture farms. During the winter of 1995-1996 in the greater Toronto area there was a cluster of four cases of invasive S. iniae infection in people who had recently handled fresh, whole fish from such farms. METHODS: We conducted a prospective and retrospective community-based surveillance for cases of S. iniae infection in humans. To obtain a large sample of isolates, we studied cultures obtained from the surface of fish from aquaculture farms. Additional isolates were obtained from the brains of infected tilapia (oreochromis species). All the isolates were characterized by pulsed-field gel electrophoresis (PFGE). RESULTS: During one year, our surveillance identified a total of nine patients with invasive S. iniae infection (cellulitis of the hand in eight and endocarditis in one). All the patients had handled live or freshly killed fish, and eight had percutaneous injuries. Six of the nine fish were tilapia, which are commonly used in Asian cooking. Thirteen additional S. iniae isolates (2 from humans and 11 from infected tilapia) were obtained from normally sterile sites. The isolates from the nine patients were indistinguishable by PFGE and were highly related to the other clinical isolates. There was substantial genetic diversity among the 42 surveillance isolates from the surface of fish, but in 10 isolates the PFGE patterns were identical to those from the patients with S. iniae infection. CONCLUSIONS: S. iniae can produce invasive infection after skin injuries during the handling of fresh fish grown by aquaculture. We identified a clone of S. iniae that causes invasive disease in both humans and fish.

Adult↗