%0 Journal Article
%T Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts
%A Aamir Nazir
%A Alkistis Manousopoulou
%A Constantin J. Pournaras
%A Emilie Falconnet
%A Emmanuelle Ranza
%A Federico A. Santoni
%A Graeme CM. Black
%A Hugo J. Bellen
%A Hyung-lok Chung
%A Inayat Shah
%A Jawad Ahmed
%A Khitab Gul
%A Maqsood A. Ansari
%A Michel Guipponi
%A Muhammad Ansar
%A Muhammad T. Sarwar
%A Periklis Makrythanasis
%A Rachel L. Taylor
%A Samina Imtiaz
%A Sondas Saeed
%J Archive of "American Journal of Human Genetics".
%D 2018
%R 10.1016/j.ajhg.2018.09.004
%X Infantile and childhood-onset cataracts form a heterogeneous group of disorders; among the many genetic causes, numerous pathogenic variants in additional genes associated with autosomal-recessive infantile cataracts remain to be discovered. We identified three consanguineous families affected by bilateral infantile cataracts. Using exome sequencing, we found homozygous loss-of-function variants in DNMBP: nonsense variant c.811C>T (p.Arg271£¿) in large family F385 (nine affected individuals; LOD score = 5.18 at ¦È = 0), frameshift deletion c.2947_2948del (p.Asp983£¿) in family F372 (two affected individuals), and frameshift variant c.2852_2855del (p.Thr951Metfs£¿41) in family F3 (one affected individual). The phenotypes of all affected individuals include infantile-onset cataracts. RNAi-mediated knockdown of the Drosophila ortholog still life (sif), enriched in lens-secreting cells, affects the development of these cells as well as the localization of E-cadherin, alters the distribution of septate junctions in adjacent cone cells, and leads to a ¡«50% reduction in electroretinography amplitudes in young flies. DNMBP regulates the shape of tight junctions, which correspond to the septate junctions in invertebrates, as well as the assembly pattern of E-cadherin in human epithelial cells. E-cadherin has an important role in lens vesicle separation and lens epithelial cell survival in humans. We therefore conclude that DNMBP loss-of-function variants cause infantile-onset cataracts in humans
%K cataract
%K DNMBP
%K Drosophila
%K still life
%K pigment cells
%K cornea
%K photoreceptors
%K bristles
%K ERG
%K eye development
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174361/