Jalili syndrome
The combination of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) was first reported as a recessively inherited trait by Jalili and Smith in 1988.
(A) Severe loss of tooth enamel due to amelogenesis imperfecta. (B) Macular atrophy.
By autozygosity mapping in families from the Middle East, Chris Inglehearn, Alan Mighell and their colleagues and collaborators have recently shown that this condition results from mutations in the CNNM4 gene on chromosome 2q11, encoding a putative metal ion transporter.
Expressed in both the retina and developing teeth, CNNM4 may play distinct roles in these two locations, regulating both an aspect of metal ion transport required for biomineralization, and some aspect of retinal photoreceptor homeostasis.
The image to the right shows immunolocalization of the murine homologue of CNNM4 (green fluorescence) to the outer and innner plexiform layers (OPL, IPL) and ganglion cell layer (GCL) of the retina.
Parry DA, Mighell AJ, El-Sayed W, Shore RC, Jalili IK, Dollfus H, Bloch-Zupan A, Carlos R, Carr IM, Downey LM, Blain KM, Mansfield DC, Shahrabi M, Heidari M, Aref P, Abbasi M, Michaelides M, Moore AT, Kirkham J, Inglehearn CF (2009). Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. Am J Hum Genet 84:266-73. Journal site
Leber congenital amaurosis is the commonest form of congenital blindness. One gene, LCA5 on Chr. 6q14, encodes the ciliary protein lebercilin. The image shows lebercilin co-localized with tubulin in cultured cells.