Homozygosity mapping of a second gene locus for hereditary combined deficiency of vitamin K-dependent clotting factors to the centromeric region of chromosome 16.

Familial multiple coagulation factor deficiency (FMFD) of factors II, VII, IX, X, protein C, and protein S is a very rare bleeding disorder with autosomal recessive inheritance. The phenotypic presentation is variable with respect to the residual activities of the affected proteins, its response to oral administration of vitamin K, and to the involvement of skeletal abnormalities. The disease may result either from a defective resorption/transport of vitamin K to the liver, or from a mutation in one of the genes encoding gamma-carboxylase or other proteins of the vitamin K cycle.

Congenital deficiency of vitamin K dependent coagulation factors in two families presents as a genetic defect of the vitamin K-epoxide-reductase-complex.

Hereditary combined deficiency of the vitamin K dependent coagulation factors is a rare bleeding disorder. To date, only eleven families have been reported in the literature. The phenotype varies considerably with respect to bleeding tendency, response to vitamin K substitution and the presence of skeletal abnormalities, suggesting genetic heterogeneity.

Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that is triggered in genetically predisposed individuals by common anesthetics and muscle relaxants. The ryanodine receptor (RYR1) is mutated in a number of MH pedigrees, some members of which also have central core disease (CCD), an inherited myopathy closely associated with MH. Mutation screening of 6 kb of the RYR1 gene has identified four adjacent novel mutations, C6487T, G6488A, G6502A, and C6617T, which result in the amino acid alterations Arg2163Cys, Arg2163His, Val2168Met, and Thr2206Met, respectively.

Genomic sequence and organization of the human gene for cytochrome c oxidase subunit (COX7A1) VIIa-M.

Cytochrome c oxidase (COX, EC 1.9.3.

A genome wide search for susceptibility loci in three European malignant hyperthermia pedigrees.

Malignant hyperthermia (MH) is an autosomal dominant disorder which is potentially lethal in susceptible individuals on exposure to commonly used inhalational anaesthetics and depolarising muscle relaxants. Crises reflect the consequences of disturbed skeletal muscle calcium homeostasis. Susceptibility was first localised to chromosome 19q13.

New mutations in the ataxia telangiectasia gene.

We report the detection of four new mutations in the ataxia telangiectasia gene (ATM). Reverse-transcribed RNA extracted from cultured cells was analysed for mutations by polymerase chain reaction amplifications and restriction endonuclease fingerprinting. Three deletions and a base substitution are described.

A complex satellite DNA polymorphism flanking the human ryanodine receptor gene (RYR1).

We describe a new highly polymorphic DNA marker flanking the human ryanodine receptor gene (RYR1) at chromosome band 19q13.1. The marker is composed of a 25bp minisatellite sequence, a compound microsatellite (AC)(AT), and an oligo-T stretch.

Sorsby's fundus dystrophy is genetically linked to chromosome 22q13-qter.

Sorsby's fundus dystrophy (SFD) is an autosomal dominant macular degeneration developing in the third or fourth decade. Patients lose central vision from subretinal neovascularization and atrophy of the choriocapillaris, pigment epithelium and retina. SFD shares some striking clinical features with age-related macular degeneration (AMD), the most common cause of blindness in western countries thereby providing a valuable genetic model for AMD.

The human gene for alkaptonuria (AKU) maps to chromosome 3q.

Alkaptonuria (AKU; McKusick no. 203500) is a rare autosomal recessive disorder caused by the lack of homogentisic acid oxidase activity. Patients excrete large amounts of homogentisic acid in their urine and a black ochronotic pigment is deposited in their cartilage and collagenous tissues.

Denial of visual perception.

An adult with the diagnosis of cortical blindness, complaining of a complete visual loss of 2 years in duration, was found to have a small preserved visual field and remarkably preserved visual abilities. Although denying visual perception, he correctly named objects, colors, and famous faces, recognized facial emotions, and read various types of single words with greater than 50% accuracy when presented in the upper right visual field. Upon confrontation regarding his apparent visual abilities, the patient continued to deny visual perceptual awareness, typically stating "I feel it.