Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two siblings suffered from Ehlers-Danlos syndrome characterized by skin fragility, joint laxity and dermal hyperelasticity. The association with microcornea and muscle hypotonia allowed the preliminary classification into type VI according to McKusick. Ultrastructure analysis of skin biopsies revealed poor integration of collagen fibrils into fibres; accordingly, the texture of the connective tissue appeared irregular. Lysyl hydroxylase activity of cultured skin fibroblasts was markedly reduced in the cells of the two patients. Preliminary studies revealed intermediate activity in the cells cultured from the skin of the parents. This finding suggested an autosomal recessive mode of inheritance. Unexpectedly and in contrast to the 3 cases reported in the literature, the hydroxylysine deficit in the patients' skin was, for reasons not yet understood, only mild. Therefore, amino acid analysis of skin is not adequate for the diagnosis of lysyl hydroxylase-deficient Ehlers-Danlos syndrome type VI.
 ...
PMID:Ehlers-Danlos syndrome in two siblings with deficient lysyl hydroxylase activity in cultured skin fibroblasts but only mild hydroxylysine deficit in skin. 118 96

The type VI variant of the Ehlers-Danlos syndrome (EDS) is a recessively inherited connective-tissue disorder. The characteristic features of the variant are muscular hypotonia, kyphoscoliosis, ocular manifestations, joint hypermobility, skin fragility and hyperextensibility, and other signs of connective-tissue involvement. The biochemical defect in most but not all patients is a deficiency in lysyl hydroxylase activity. Lysyl hydroxylase is an enzyme that catalyzes the formation of hydroxylysine in collagens and other proteins with collagen-like amino acid sequences. We have recently reported an apparently homozygous large-duplication rearrangement in the gene for lysyl hydroxylase, leading to the type VI variant of EDS in two siblings. We now report an identical, apparently homozygous large duplication in an unrelated 49-year-old female originally analyzed by Sussman et al. Our simple-sequence-repeat-polymorphism analysis does not support uniparental isodisomy inheritance for either of the two duplications. Furthermore, we indicate in this study that the duplication in the lysyl hydroxylase gene is caused by an Alu-Alu recombination in both families. Cloning of the junction fragment of the duplication has allowed synthesis of appropriate primers for rapid screening for this rearrangement in other families with the type VI variant of EDS.
 ...
PMID:Alu-Alu recombination results in a duplication of seven exons in the lysyl hydroxylase gene in a patient with the type VI variant of Ehlers-Danlos syndrome. 797 51

Two unrelated girls, aged 11 and 14 years, with clinical manifestations of Ehlers-Danlos syndrome (EDS) type VIB, characteristic facies, skeletal abnormalities, and other features are described. They had Marfanoid habitus with pectus excavatum; fragile, hyperextensible, and readily bruisable skin with widened, atrophic scars; recurrent hematomas; generalized joint laxity; hypotonia; scoliosis; and mild delay of gross motor development. Lysyl hydroxylase deficiency was ruled out in Patient 1. Parental consanguinity was present in Patient 2. They both had, in early childhood, down-slanting palpebral fissures, drooping lower eyelids, short nose, small mouth, and long philtrum. Facial features that persisted included thick eyebrows, hypertelorism, strabismus, blue sclerae, low-set, and slanted ears, hypoplastic columella, high-arched palate, and thin upper lip. They had tubular stenosis of the phalanges, metacarpals, and metatarsals; decreased physiological curvatures of the spinal column with tall vertebrae; and joint contractures including talipes equinovarus and progressive talipes valgus. Their hearing of high-pitched sounds was impaired. They had constipation and recurrent cystitis with an enlarged bladder. In view of these findings, we propose that these two girls represent a clinically recognizable subgroup of EDS type VIB.
 ...
PMID:Ehlers-Danlos syndrome type VIB with characteristic facies, decreased curvatures of the spinal column, and joint contractures in two unrelated girls. 1615 41