Proximal renal tubular acidosis and ocular pathology: a novel missense mutation in the gene (SLC4A4) for sodium bicarbonate cotransporter protein (NBCe1).

Purpose: The electrogenic Na+/HCO3- cotransporter (NBCe1) plays a major role in renal bicarbonate absorption via proximal tubules and therefore is crucial for maintaining normal blood pH. The human gene for NBCe1 (SLC4A4) produces two major transcripts by alternative promoter usage (kNBCe1, originally cloned from kidney and pNBCe1, pancreatic/general form). Though rare, recessive SLC4A4 mutations have been reported in patients with proximal renal tubular acidosis, short stature, and ocular pathology.

A novel RPGR exon ORF15 mutation in a family with X-linked retinitis pigmentosa and Coats'-like exudative vasculopathy.

Purpose: To describe the ophthalmic and genetic findings in a family with X-linked retinitis pigmentosa (RP) and Coats'-like exudative vasculopathy.

Design: Observational case series.

Methods: Family members underwent comprehensive ophthalmologic examination.

Susceptibility genes for age-related maculopathy on chromosome 10q26.

On the basis of genomewide linkage studies of families affected with age-related maculopathy (ARM), we previously identified a significant linkage peak on 10q26, which has been independently replicated by several groups. We performed a focused SNP genotyping study of our families and an additional control cohort. We identified a strong association signal overlying three genes, PLEKHA1, LOC387715, and PRSS11.

Meta-analysis of genome scans of age-related macular degeneration.

A genetic contribution to the development of age-related macular degeneration (AMD) is well established. Several genome-wide linkage studies have identified a number of putative susceptibility loci for AMD but only a few of these regions have been replicated in independent studies. Here, we perform a meta-analysis of six AMD genome screens using the genome-scan meta-analysis method, which allows linkage results from several studies to be combined, providing greater power to identify regions that show only weak evidence for linkage in individual studies.

Histopathologic study of X-linked cone-rod dystrophy (CORDX1) caused by a mutation in the RPGR exon ORF15.

Purpose: To evaluate the donor retina of a patient with X-linked cone-rod dystrophy caused by an RPGR exon ORF15 mutation.

Design: Histopathologic study of the retina.

Methods: The eye of a 69-year-old man was fixed at 1.

A presumed missense mutation of RPGR causes abnormal RNA splicing with exon skipping.

Purpose: A patient with retinitis pigmentosa demonstrated a novel RPGR mutation (213G>A, last base of exon 2) predicted to cause a missense change (G52R) in the final protein. This study was performed to determine whether this mutation altered the effectiveness of the adjacent splice site.

Design: Observational case report.

A novel compound heterozygous mutation in the cellular retinaldehyde-binding protein gene (RLBP1) in a patient with retinitis punctata albescens.

Purpose: To describe a patient with retinitis punctata albescens (RPA) associated with compound heterozygosity for two novel mutations in the RLBP1 encoding cellular retinaldehyde-binding protein (CRALBP).

Design: Observational case report.

Methods: The proband underwent a complete ophthalmic examination and leukocyte genomic DNA samples were obtained from him and his parents.

Age-related maculopathy: a genomewide scan with continued evidence of susceptibility loci within the 1q31, 10q26, and 17q25 regions.

Age-related maculopathy (ARM), or age-related macular degeneration, is one of the most common causes of visual impairment in the elderly population of developed nations. In a combined analysis of two previous genomewide scans that included 391 families, containing up to 452 affected sib pairs, we found linkage evidence in four regions: 1q31, 9p13, 10q26, and 17q25. We now have added a third set of families and have performed an integrated analysis incorporating 530 families and up to 736 affected sib pairs.

Fluorescein-potentiated argon laser therapy improves symptoms and appearance of corneal neovascularization.

Purpose: To evaluate patients' self-assessment of their symptoms and cosmetic appearance after fluorescein-potentiated argon laser treatment (FPAL) for corneal inflammation associated with neovascularization. To describe the objective effects of FPAL therapy on established corneal neovascularization with secondary corneal edema and lipid keratopathy.

Methods: Fifteen patients with corneal neovascularization resulting from various infectious and traumatic etiologies were enrolled in an open, nonrandomized pilot study.

A tale of two genotypes: consistency between two high-throughput genotyping centers.

Multiple genome-wide scans involving sib-pairs or limited pedigrees have been extensively used for a wide number of complex genetic conditions. Comparing data from two or more scans, as well as combining data, require an understanding of the sources of genotyping errors and data discrepancies. We have conducted two genome-wide scans for age-related maculopathy using the Center for Inherited Disease Research (CIDR) and the Mammalian Genotyping Service (MGS).

X-linked cone-rod dystrophy (locus COD1): identification of mutations in RPGR exon ORF15.

X-linked cone-rod dystrophy (COD1) is a retinal disease that primarily affects the cone photoreceptors; the disease was originally mapped to a limited region of Xp11.4. We evaluated the three families from our original study with new markers and clinically reassessed all key recombinants; we determined that the critical intervals in families 2 and 3 overlapped the RP3 locus and that a status change (from affected to probably unaffected) of a key recombinant individual in family 1 also reassigned the disease locus to include RP3 as well.