Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a 33-year-old male patient with mental retardation and cerebellar ataxia whose brain magnetic resonance imaging (MRI) showed diffuse central hypomyelination. The associated hypogonadotropic hypogonadism and hypodontia were consistent with the clinical diagnosis of 4H syndrome. Two compound heterozygous mutations in POLR3A were found: p.Met852Val and p.Asn1249His. MRI of the brain showed cerebellar atrophy, atrophy of the corpus callosum, and diffuse hypomyelination extending as far as the U-fibers, with preservation of the basal ganglia. T2 hyperintensity was observed in the bilateral middle cerebellar peduncles. The patient showed almost normal development until 4-5years of age. After 25years of age, the patient showed a gradual but consistent motor and cognitive deterioration. We demonstrated the involvement of the corticospinal tract electrophysiologically, but peripheral nerve conduction was normal. Although this disease may start very early in life, the clinical course in the present case suggests that brains that initially appear to have developed normally may show dysfunction later in life, although the pathophysiological bases for this dysfunction may not be evident on MRIs.
 ...
PMID:Diffuse central hypomyelination presenting as 4H syndrome caused by compound heterozygous mutations in POLR3A encoding the catalytic subunit of polymerase III. 2281 58

We describe a 27-year-old man with mental retardation, symptomatic epilepsy, myopia, and cerebellar ataxia without spontaneous puberty whose brain magnetic resonance imaging showed hypomyelination. He had child-like facial appearance, with thin facial hair. He had no underarm and pubic hairs, and his penis was small. Laboratory tests showed low levels of luteinizing hormone, follicle-stimulating hormone, and testosterone. Brain MRI showed diffuse hypomyelination, atrophy of the cerebellum and brainstem, and hypoplastic corpus callosum. Ictal N-isopropyl-p-(indone-123)-iodoamphetamine single photon emission computed tomography (<sup>123</sup>I-IMP SPECT) revealed hypoperfusion of bilateral frontal cingulate and temporal lobe and cerebellar hemispheres. Homozygous missense mutation c.2350G>A was found in POLR3A and the patient was diagnosed with Pol III-related leukodystrophy, which is a rare disease. We describe the present case in light of the characteristics of the past reports in Japan. (Received April 5, 2016: Accepted June 30, 2016; Published November 1, 2016).
 ...
PMID:[A Case of Pol III-related Leukodystrophy with Homozygous Mutation in POLR3A]. 2785 30