What's new AAPOS 2008 - The Private Eye Clinic

Clinical expression of Leber hereditary optic neuropathy is affected by the
mitochondrial DNA – Haplogroup background.
Hudson G, Carelli V, Spruijt L, Gerards M, et al.
Am. J. Hum. Genet 2007; 81:228-233.
The author present 2 alternative: 1) to use an LCA diagnosis only in patients in whom
there are absolutely no other signs of systemic or neurological abnormalities, and to
assign all others to the respective syndromes; or 2)change the terminology from LCA to
LCAOP (LCA ocular phenotype) to include initially all patients with this blinding ocular
condition, with the understanding that the diagnosis could be changed to LCA or that of
a more specific systemic one as other manifestations of the disease become more
manifest.
Novel compound heterozygous TULP1 mutations in a family with severe earlyonset
retinitis pigmentosa.
Anneke den Hollander PhD, Janneke van Lith-Verhoeven MD, Maarten Arends BSc,
Tim Strom MD PhD, Frans Cremers PhD, Carel Hoyng MD PhD
Arch Ophthalmol 2007;125(7):932-935
This study confirms that TULP1 mutations cause a severe early-onset form of
autosomal recessive retinitis pigmentosa. Members of a Surinamese family with
autosomal recessive retinitis pigmentosa underwent blood sampling and ophthalmologic
examinations. All affected family members had a severe retinal dystrophy with history
of nystagmus, low visual acuity, and nyctalopia since infancy. The scotopic and
photopic responses were nonrecordable on electroretinography. A genome-wide scan
suggested linkage to the chromosomal region containing the TULP1 gene. Mutation
analysis of TULP1 identified novel compound heterozygous mutations in all affected
family members.
Blue eye color in humans may be caused by a perfectly associated founder
mutation in a regulatory element located within the HERC2 gene inhibiting OCA2
expression
Eiberg H, Troelsen J, Neilsen M, Mikkelsen A et al.
Hum Genet 2008; Jan 3 [Epub, ahead of print]
Human eye color is a quantitative trait displaying multifactorial inheritance. The locus
responsible for the brown or blue eye phenotypes is 15q. Subsequent studies have
shown that the OCA2 locus is the major contributor to the human eye color variation.
The authors’ present evidence, from linkage and association studies, that a region in
HERC2 contains a highly conserved regulatory element, which is the cause of blue eye
color in humans. (They analyzed data from a three-generation Danish family. Only
families with siblings, who had blue and brown eyes, were included in the study). This
element had an inhibitory effect on the OCA2 promoter activity in cell cultures, and the
blue and the brown alleles were shown to bind non-identical subsets of nuclear extracts.
62