Biomedical subjects

D Daentl

Publications and source records attributed to D Daentl.

3 recordsLinked to original sources

PubMed2001

EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy.

Heterozygous mutations in the early growth response gene 2 (EGR2), which encodes a zinc-finger transcription factor that regulates the late stages of myelination, cause myelinopathies including congenital hypomyelinating neuropathy, Dejerine-Sottas neuropathy (DSN), and Charcot-Marie-Tooth disease type 1. We screened 170 unrelated neuropathy patients without mutations involving the peripheral myelin protein 22 gene (PMP22), the myelin protein zero gene (MPZ), or the gap junction protein beta1 gene (GJB1) and identified two DSN patients with the heterozygous mutation R359W in the alpha-helix domain of the first zinc-finger of EGR2. We now report that this mutation is a recurrent cause of DSN, and that expressivity ranges from that typical for DSN to a more rapidly progressive neuropathy that can cause death by age 6 years. Furthermore, in contrast to patients with typical DSN, patients with the EGR2 R359W mutation have more respiratory compromise and cranial nerve involvement.

Amino Acid Substitution↗

PubMed1999

Calpain III mutation analysis of a heterogeneous limb-girdle muscular dystrophy population.

OBJECTIVE: To determine the frequency of calpain III mutations in a heterogeneous limb-girdle muscular dystrophy (LGMD) population. BACKGROUND: Mutations of the calpain III gene have been shown to cause a subset of autosomal recessive LGMDs. Patient populations studied to date have been primarily of French and Spanish origin, in which calpain III may cause 30% of autosomal recessive MDs. The incidence of calpain III mutations in non-French/Spanish MD patients has not been studied thoroughly. No sensitive and specific biopsy screening methods for detecting patients with abnormal calpain III protein are available. Thus, detection of patients relies on direct detection of gene mutations. METHODS: The authors studied the calpain III gene in 107 MD patient muscle biopsies exhibiting normal dystrophin. Muscle biopsy RNA was produced for each patient, and the entire calpain III complementary DNA was screened for mutations by reverse-transcriptase PCR/single-strand conformation polymorphism using three different conditions. RESULTS: The authors identified nine patients (eight unrelated) with causative mutations. Six of the seven distinct mutations identified are novel mutations and have not been described previously. CONCLUSION: The results suggest that approximately 9.2% of patients in the heterogeneous population with an LGMD diagnosis will show mutations of the calpain III gene. Interestingly, two patients were heterozygous for a single mutation at the DNA level, whereas only the mutant allele was observed at the RNA level. This suggests that there are undetectable, nondeletion mutations that ablate expression of the calpain III gene.

Adolescent↗

PubMed1978

Hyaline cartilage changes in diastrophic dwarfism.

Hyaline cartilage of the talus of a diastrophic dwarf was studied by light and transmission electron microscopy before and after proteoglycan extraction or digestion, glycogen digestion, and enzyme marking. The nuclei of the chondrocytes were as a rule large and round and the cytoplasm contained large vacuoles. Best's carmine stained the cytoplasm of most cells red; after diastase digestion the cytoplasm remained unstained. This suggested that the cells contained glycogen. This observation was complimented by the ultrastructural demonstration of large amounts of glycogen. Cell scars were frequent. The shape and state of activity of the cells as well as the development of intracytoplasmic organelles showed great variability. The matrix showed many areas of degeneration and a general dearth of sulphated acid mucopolysaccharides. A lacey pattern of unmasked collagen fibers was frequently seen. Collagen fibers showed a great variability in diameter and often appeared frayed when examined by electron microscopy. These observations suggest an enzymatic deficiency in chondrocyte mucopolysaccharide and glucose metabolism. The techniques we used when added to biochemical studies should prove useful in the investigation of human dwarfism.

Cartilage↗