Subject(s)
Ammonia/blood , Ornithine Carbamoyltransferase/genetics , Age of Onset , Amino Acid Substitution , Base Sequence , Child , Child, Preschool , Family Health , Fatal Outcome , Female , Humans , Infant, Newborn , Introns/genetics , Male , Ornithine Carbamoyltransferase Deficiency Disease , Point Mutation , Sequence DeletionABSTRACT
Retinitis pigmentosa (RP) is a group of progressive hereditary disorders of the retina in which various modes of inheritance have been described. Here, we report on X linked RP in nine families with constant and severe expression in carrier females. In our series, however, the phenotype was milder and delayed in carrier females compared to hemizygous males. This form of X linked RP could be regarded therefore as partially dominant. The disease gene maps to chromosome Xp2.1 in the genetic interval encompassing the RP3 locus (Zmax=13.71 at the DXS1100 locus). Single strand conformation polymorphism and direct sequence analysis of the retinitis pigmentosa GTPase regulator (RPGR) gene, which accounts for RP3, failed to detect any mutation in our families. Future advances in the identification of X linked RP genes will hopefully help to elucidate the molecular basis of this X linked dominant RP.
Subject(s)
Carrier Proteins/genetics , Eye Proteins , Genetic Linkage , Heterozygote , Retinitis Pigmentosa/genetics , X Chromosome , Adolescent , Adult , Arginine , Child , Child, Preschool , Chromosome Mapping , Female , Genetic Markers , Humans , Isoleucine , Male , Middle Aged , Pedigree , Polymorphism, Genetic , Polymorphism, Single-Stranded ConformationalSubject(s)
Ammonia/blood , Metabolism, Inborn Errors/genetics , Multigene Family , Ornithine Carbamoyltransferase/genetics , Point Mutation , Age of Onset , Female , Humans , Infant, Newborn , Liver/enzymology , Male , Metabolism, Inborn Errors/blood , Ornithine Carbamoyltransferase/metabolism , Sequence DeletionSubject(s)
Ammonia/blood , Coma/etiology , Exons , Ornithine Carbamoyltransferase/genetics , Sequence Deletion , Adolescent , Age of Onset , Coma/genetics , Female , Glutamic Acid , Humans , Male , Ornithine Carbamoyltransferase Deficiency Disease , Pedigree , Polymerase Chain Reaction , Reading FramesABSTRACT
Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder of the urea cycle mapped to chromosome Xp21.1. Here, we show that apparent segregation of null alleles at the OTC locus and flanking polymorphic loci mimicked false maternity or false paternity in three affected families. Based on these observations, we suggest giving consideration to gene deletion when dealing with segregation of null alleles in OTC deficiency.
Subject(s)
Alleles , Ammonia/blood , Gene Deletion , Ornithine Carbamoyltransferase Deficiency Disease , Ornithine Carbamoyltransferase/genetics , Female , Humans , Infant, Newborn , Male , Pedigree , X ChromosomeSubject(s)
Amino Acid Metabolism, Inborn Errors/genetics , Exons , Ornithine Carbamoyltransferase/genetics , Point Mutation , Age of Onset , Amino Acid Metabolism, Inborn Errors/enzymology , Amino Acid Metabolism, Inborn Errors/epidemiology , Amino Acid Sequence , Ammonia/blood , Base Sequence , Child , DNA, Single-Stranded/genetics , Fatal Outcome , Genes , Humans , Infant , Kinetics , Liver/enzymology , Male , Molecular Sequence Data , Nucleic Acid Conformation , Ornithine Carbamoyltransferase Deficiency Disease , Polymorphism, Genetic , Sequence AlignmentABSTRACT
Juvenile retinoschisis (RS) is an X linked recessive vitreoretinal disorder for which the basic molecular defect is unknown. The gene for RS has been previously localised by linkage analysis to Xp22.1-p22.2 and the locus order Xpter-DXS16-(DXS43, DXS207)-RS-DXS274-DXS41-Xcen established. To improve the resolution of the genetic map in the RS region, we have isolated a highly polymorphic microsatellite at DXS207, which displays at least nine alleles with a heterozygosity of 0.83. Using this microsatellite and four other Xp22.1-p22.2 marker loci, DXS16, DXS43, DXS274, and DXS41, we performed pairwise and multilocus linkage analysis in 14 kindreds with RS. The microsatellite was also typed in the CEPH (Centre d'Etude du Polymorphisme Humain) reference families. Tight linkage was found between RS and DXS207 (Z(theta) = 14.32 at theta = 0.0), RS and DXS43 (Z(theta) = 8.10 at theta = 0.0), and DXS207 and DXS43 (Z(theta) = 40.31 at theta = 0.0). Our linkage results combined with data previously reported suggest that the DXS207-DXS43 cluster is located less than 2 cM telomeric to the RS locus. The microsatellite reported here will be a very useful marker for further linkage studies with retinoschisis as well as with other diseases in this region of the X chromosome.
