Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The congenital muscular dystrophies (CMD) constitute a clinically and genetically heterogeneous group of autosomal recessive myopathies. Patients show congenital hypotonia, muscle weakness, and dystrophic changes on muscle biopsy. Mutations in four genes (FKT1, POMGnT1, POMT1, FKRP) encoding putative glycosyltransferases have been identified in a subset of patients characterized by a deficient glycosylation of alpha-dystroglycan on muscle biopsy. FKRP mutations account for a broad spectrum of patients with muscular dystrophy, from a severe congenital form with or without mental retardation (MDC1C) to a much milder limb-girdle muscular dystrophy (LGMD2I). We identified two novel homozygous missense FKRP mutations, one, A455D, in six unrelated Tunisian patients and the other, V405L, in an Algerian boy. The patients, between the ages of 3 and 12 years, presented with a severe form of MDC1C with calf hypertrophy and high serum creatine kinase levels. None had ever walked. Two had cardiac dysfunction and one strabismus. They all had mental retardation, microcephaly, cerebellar cysts, and hypoplasia of the vermis. White matter abnormalities were found in five, mostly when cranial magnetic resonance imaging was performed at a young age. These abnormalities were shown to regress in one patient, as has been observed in patients with Fukuyama CMD. Identification of a new microsatellite close to the FKRP gene allowed us to confirm the founder origin of the Tunisian mutation. These results strongly suggest that particular FKRP mutations in the homozygous state induce structural and clinical neurological lesions in addition to muscular dystrophy. They also relate MDC1C to other CMD with abnormal protein glycosylation and disordered brain function.
 ...
PMID:New FKRP mutations causing congenital muscular dystrophy associated with mental retardation and central nervous system abnormalities. Identification of a founder mutation in Tunisian families. 1465 96

Congenital muscular dystrophy type 1C (MDC1C) is caused by the homozygous or compound heterozygous mutations of the FKRP gene. This article reported the clinical and mutation features of a child with MDC1C. The boy aged 8 months visited the hospital due to delayed development. As for clinical manifestations, the boy could not turn over or sit stably by himself, and there was a significant reduction in muscle tension; biceps reflex in both upper extremities and patellar tendon reflex and Achilles tendon reflex in both lower extremities could not be induced. The boy also had a stereotyped facial expression and strabismus. Gene detection revealed c.350C>G and c.1303C>T compound heterozygous mutations in the FKRP gene. The c.350C>G mutation came from the mother and had been reported as a pathogenic missense mutation. The c.1303C>T mutation came from the father and was a new missense mutation, and a bioinformatics analysis showed that it might be a pathogenic mutation. The boy was diagnosed with MDC1C with reference to the clinical features of hypotonia and motor developmental delay and FKRP gene mutation sequencing.
 ...
PMID:[Clinical features and FKRP mutations of congenital muscular dystrophy 1C]. 3021 31