Identification of Novel Mutations in Patients with Leber Congenital Amaurosis and Juvenile RP by Genome-wide Homozygosity Mapping with SNP Microarrays

Abstract

Homozygosity mapping using SNP microarrays identified mutations in a significant proportion (30%) of consanguineous patients with LCA and juvenile RP and in a small number (3%) of nonconsanguineous patients. Significant homozygous regions which did not map to known LCA or juvenile RP genes and may be instrumental in identifying novel disease genes were detected in 33 patients.

TULP1Mutations Causing Early-Onset Retinal Degeneration: Preserved but Insensitive Macular Cones

“…[8][9][10][11][12][13][62][63][64] The remainder categorize the disease as arRP, but note childhoodonset vision loss and night blindness. 14,62,[65][66][67][68] Regardless of clinical diagnosis, early-onset night blindness, visual acuity loss and nystagmus are common findings. To our knowledge, there are no reports of patients with TULP1 mutations who have onset of symptoms in the second or third decades of life.…”

“…Ophthalmoscopic features reported were those of other widespread retinal degenerations: vessel attenuation, waxy disc pallor, and RPE changes and/or atrophy; less common were mentions of maculopathy and a central retinal annulus of yellow deposits. 4,7,10,12,13,62,63,66,68,69 As for visual function, there are only five patients in the literature to date with visual acuities between 20/30 and 20/70 at evaluation 14,62,69 ; all others had worse than 20/100. Kinetic visual fields (to large bright targets) could be preserved in early childhood, but peripheral field was lost in later life.…”

“…Kinetic visual fields (to large bright targets) could be preserved in early childhood, but peripheral field was lost in later life. 4,7,62 Rod and cone function assayed by ERG has mainly shown no detectable responses; there is one mention of a rod-cone pattern. 62 Dark-adapted two-color perimetry in our study of the Dominican population indicated no measurable rod function; the retained central vision was cone-mediated.…”

“…4,7,62 Rod and cone function assayed by ERG has mainly shown no detectable responses; there is one mention of a rod-cone pattern. 62 Dark-adapted two-color perimetry in our study of the Dominican population indicated no measurable rod function; the retained central vision was cone-mediated. There were also microvolt-level cone flicker ERGs remaining in some of these patients.…”

Identification of Mutations Causing Inherited Retinal Degenerations in the Israeli and Palestinian Populations Using Homozygosity Mapping

“…Homozygous mutations usually are detected in patients of consanguineous parents, but also can be found in patients from relatively isolated populations, where the chance of the parents being distant relatives is high, but cannot be traced by the available family history. [3][4][5] On the other hand, one also should bear in mind that in some cases patients of consanguineous marriages are not homozygous for the disease-causing mutation, but rather are compound heterozygous and homozygosity mapping might be misleading in such families. [6][7][8] The Palestinian and Israeli populations include a large number of subpopulations (e.g., Jews, Arab-Muslims, ArabChristians, Bedouin, and Druze) with a relatively high frequency of consanguineous marriages and marriages between members of relatively isolated subpopulations.…”