Usher syndrome (USH) refers to genetically and clinically heterogeneous autosomal recessive disorders with combined visual and hearing loss. Type I (USH1) is characterized by a congenital, severe to profound hearing loss and absent vestibular function; in type II (USH2) the hearing loss is congenital and moderate to severe, and the vestibular function is normal. Progressive pigmentary retinopathy (PPR) is present in both types. A third type (USH3) differing from USH2 by the progressive nature of its hearing loss has been suggested. USH3 has previously been estimated to comprise 2% of all USH. However, based on clinical criteria, in Finland 42% of USH patients have progressive hearing loss suggesting enrichment of an USH3 gene. We excluded the four previously mapped USH regions as the site of the USH3 disease locus. Systematic search for USH3 by genetic linkage analyses in 10 multiple affected families using polymorphic microsatellite markers revealed significant linkage with markers mapping to chromosome 3q. Pairwise lod scores at zero recombination distance were 7.87 for D3S1308, and 11.29 for D3S1299, incorporating the observed linkage disequilibrium. Conventional multipoint linkage analysis gave a maximum lod score of 9.88 at D3S1299 assigning USH3 to the 5 cM interval between markers D3S1555 and D3S1279 in 3q21-25.(ABSTRACT TRUNCATED AT 250 WORDS)
Choroideremia (CHM) is an X-linked progressive degeneration of the choroid and retina. 12% of unrelated male patients carry deletions of the partially cloned CHM gene. In Finland, there are more than 120 living CHM patients belonging to eight apparently unrelated pedigrees. Molecular deletions involving the CHM gene have been detected in three families. We have screened the remaining five families for point mutations. In one large family a single nucleotide (T) insertion into the donor splice site of exon C leads to two aberrantly spliced mRNAs both producing a premature stop codon. The mutation can be assayed easily by amplification and digestion with Msel. Our findings provide additional evidence for the pathogenetic role of CHM mutations and provide a diagnostic tool for one fifth of the world's known CHM patients.
Urinary and plasma amines and amine metabolites were quantified in two individuals with Norrie disease resulting from a deletion in chromosomal region Xp11.3, recently reported to be associated with absence of the gene encoding monoamine oxidase (MAO)-A and nondetectable MAO-A activity in fibroblasts and MAO-B activity in platelets. Marked (four-to 100-fold) elevations in levels of urinary phenylethylamine, o-tyramine, and m-tyramine (which are preferential substrates for MAO-B) and marked reductions (90%) in levels of 3-methoxy-4-hydroxyphenylglycol (a deaminated metabolite of norepinephrine, a preferential substrate for MAO-A) in urine and plasma confirmed the presence of a systemic, functionally significant reduction in the activities of both MAO isozymes. The magnitude of these changes, which are equivalent to those found in subjects taking MAO-inhibiting antidepressants, suggests that early initiation of dietary and drug restrictions may be clinically important in these and other patients with X-chromosomal mutations involving MAO. These findings further support the proposition that the MAOA and MAOB genes are located in close proximity on the X chromosome. Negligible changes in the metabolites of dopamine and serotonin raise the possibility that other metabolic pathways are of importance for their production, that dietary or intestinal bacterial sources contribute substantially to the presence of these amine metabolites in urine, or both.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.