Bilateral retinal hemorrhages following finger pressure against the soft palate (الترفيع) in recessive <i>CRB1</i>-related retinopathy

<p><i>Purpose</i>: To report two siblings with <i>CRB1</i>-related retinopathy who developed retinal hemorrhages following village traditional treatment of upward finger pressure against the soft palate ().</p> <p><i>Methods</i>: A retrospective case series.</p> <p><i>Results</i>: Two sisters were clinically diagnosed and genetically confirmed to have recessive <i>CRB1</i>-related retinal dystrophy. The family did not accept the condition as non-treatable and took both sisters for a traditional village therapy, consisting of several sessions of intense upward index finger pressure by the healer against the soft palate for each child. When examined following this therapy, both sisters had bilateral pre-retinal hemorrhages which were not present before the intervention and resolved without sequelae over the next several months.</p> <p><i>Conclusions</i>: The traditional village therapy may have compromised retinal venous outflow and/or provoked a Valsalva phenomenon, leading to the bilateral retinal hemorrhages. The fact that this occurred bilaterally and in both sisters supports the concept of relative vessel wall incompetence as part of <i>CRB1</i>-related retinopathy.</p

Two-point LOD scores of chromosome 11q markers for families A) PKCC001 and B) PKCC113.

<p>The asterisk indicates marker included in the genome-wide scan.</p

Sequence chromatograms of causal mutations identified in PKCC001 and PKCC113.

<p>Sequence chromatograms of A) Unaffected individual 15 homozygous for wild-type allele; B) unaffected individual 17 heterozygous and C) affected individual 19, homozygous for c.34C>T (p.R12C). Sequence chromatograms of D) unaffected individual 6 homozygous for wild-type allele, E) unaffected individual 8 heterozygous and F) affected individual 10 homozygous for c.31C>T (p.R11C). The arrows point to c.31C and c.34C of <i>CRYAB</i> mutated in PKCC113 and PKCC001, respectively. It is worth to note that mutations identified in PKCC001 and PKCC113 are adjacent amino acids i.e. Arg11, and Arg12.</p

Expression profile of alpha-crystallin in developing mouse lens.

<p>The expression of <i>Cryaa</i> (blue) and <i>Cryab</i> (orange) at different developmental time points was normalized to <i>Gapdh</i>. A logarithmic trend line (red) fits the <i>Cryab</i> expression with an R² value of 0.7742. The x-axis and y-axis represent developmental time points and normalized expression of each mRNA, respectively.</p

Slit lamp photographs of individual 19 of family PKCC001 illustrating nuclear cataracts.

<p>Slit lamp photographs of individual 19 of family PKCC001 illustrating nuclear cataracts.</p

Sequence alignment of <i>CRYAB</i> in mammalian orthologues illustrating the conservation of Arginine at positions 11 and 12.

<p>Primates, Euarchontoglires, Laurasiatheria, and Afrotheria are colored brown, green, purple and orange, respectively.</p

Pedigree drawing of family PKCC025 with haplotypes of chromosome 22q microsatellite markers.

<p>Alleles forming the risk haplotype are shaded black, and alleles not co-segregating with cataracts are shown in white. Squares: males; circles: females; filled symbols: affected individuals; double line between individuals: consanguineous mating; and a diagonal line through a symbol: deceased person.</p

Expression profile of β-crystallin in the developing mouse lens.

<p>The expression of <i>Crybb1</i>, <i>Crybb2</i>, and <i>Crybb3</i> at different developmental time points was normalized to <i>Gapdh</i>. The x-axis and y-axis represent developmental time points and normalized expression of each mRNA, respectively.</p

Slit lamp photograph illustrating nuclear cataracts present in affected individual 15 of family PKCC025.

<p>Slit lamp photograph illustrating nuclear cataracts present in affected individual 15 of family PKCC025.</p

Sequence chromatograms of the c.493G>C (p.Gly165Arg) variation identified in families PKCC063, PKCC131, and PKCC168.

<p>A), D), & G) individuals 18, 7, and 12 of PKCC063, PKCC131, and PKCC168, respectively, homozygous for the wild-type allele; B), E), & H) individuals 19, 8, and 13 of PKCC063, PKCC131, and PKCC168, respectively, heterozygous, and C), F), & I) individuals 20, 9, and 14 of PKCC063, PKCC131, and PKCC168, respectively, homozygous for c.493G>C (p. Gly165Arg).</p