NMNAT1 mutations cause Leber congenital amaurosis

Leber congenital amaurosis (LCA) is an infantile-onset form of inherited retinal degeneration characterized by severe vision loss. Two-thirds of LCA cases are caused by mutations in 17 known disease-associated genes (Retinal Information Network (RetNet)). Using exome sequencing we identified a homozygous missense mutation (c.25G>A, p.Val9Met) in NMNAT1 that is likely to be disease causing in two siblings of a consanguineous Pakistani kindred affected by LCA. This mutation segregated with disease in the kindred, including in three other children with LCA. NMNAT1 resides in the previously identified LCA9 locus and encodes the nuclear isoform of nicotinamide mononucleotide adenylyltransferase, a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD(+)) biosynthesis. Functional studies showed that the p.Val9Met alteration decreased NMNAT1 enzyme activity. Sequencing NMNAT1 in 284 unrelated families with LCA identified 14 rare mutations in 13 additional affected individuals. These results are the first to link an NMNAT isoform to disease in humans and indicate that NMNAT1 mutations cause LCA.     

Effect of exogenous application of nucleic acids and auxin on the rooting of hypocotyl cuttings ofImpatiens balsamina. Evidence for the uptake of information molecules

Summary Exogenously supplied DNA and RNA hastened root initiation and also increased the formation of roots on hypocotyl cuttings ofImpatients balsamina with intact apex and cotyledons. IAA appreciably increased the nucleic acid-caused enhancement in root formation. In combination with lowe concentrations of nucleic acids, it event stimulated the growth of roots as well as of hypocotyls. Higher concentrations of nucleic acids were, however, toxic.The research has been partly financed by a grant from the United States Department of Agriculture. One of us (SB) is thankful to the Deparmtent of Atomic Engery of the Government of India for financial assistance.     

Enzymes of non-agglutinable vibrios and their possible role in the development of enterotoxic factor

Résumé Sachant que le facteur entérotoxique peut être développé dans les vibrions non-agglutinables par transfer animal, nous avons déterminé les activités enzymatiques (mucinase, protéase, lécithinase) de ces vibrions. Après ce transfert l'activité lécithinasique a augmenté, et cette activité est semblable à celle d'un virus (V. cholerae). Nous supposons que l'augmentation du facteur entérotoxique est causée par celle de l'activité de la lécithinase.

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Thanks are due to Dr.A. Mondal for help and Mr.Manzar Alam for his secretarial assistance.     

OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28

Autosomal dominant optic atrophy (ADOA) is the most prevalent hereditary optic neuropathy resulting in progressive loss of visual acuity, centrocoecal scotoma and bilateral temporal atrophy of the optic nerve with an onset within the first two decades of life. The predominant locus for this disorder (OPA1; MIM 165500) has been mapped to a 1.4-cM interval on chromosome 3q28-q29 flanked by markers D3S3669 and D3S3562 (ref. 3). We established a PAC contig covering the entire OPA1 candidate region of approximately 1 Mb and a sequence skimming approach allowed us to identify a gene encoding a polypeptide of 960 amino acids with homology to dynamin-related GTPases. The gene comprises 28 coding exons and spans more than 40 kb of genomic sequence. Upon sequence analysis, we identified mutations in seven independent families with ADOA. The mutations include missense and nonsense alterations, deletions and insertions, which all segregate with the disease in these families. Because most mutations probably represent null alleles, dominant inheritance of the disease may result from haploinsufficiency of OPA1. OPA1 is widely expressed and is most abundant in the retina. The presence of consensus signal peptide sequences suggests that the product of the gene OPA1 is targeted to mitochondria and may exert its function in mitochondrial biogenesis and stabilization of mitochondrial membrane integrity.