current
NMNAT1:c.25G>A (p.Val9Met) AND Leber congenital amaurosis 9
current
classified by single submitter
Pathogenic
germline
human
not provided
curation
In 3 sibs and 2 cousins from a consanguineous Pakistani pedigree with Leber congenital amaurosis (LCA9; 608553), Falk et al. (2012) identified homozygosity for a 25G-A transition in exon 2 of the NMNAT1 gene, resulting in a val9-to-met (V9M) substitution at a highly conserved residue. The mutation segregated with disease in the pedigree and was not found in 501 controls or in any public databases. Only 1 of the affected individuals had isolated LCA; 3 of the other LCA patients also had congenital deafness, and in those patients as well as in 2 other family members with congenital deafness, homozygosity for a nonsense mutation in the GJB2 gene (W24X; 121011.0003) known to cause deafness (see DFNB1A, 220290) was identified. Additional features in 4 of the LCA patients included global developmental delay and autism; Falk et al. (2012) stated that those presentations likely had a separate genetic etiology from that of LCA and deafness in this pedigree.
22842227
NMNAT1:c.25G>A (p.Val9Met)
NM_022787.3:c.25G>A
NG_032954.1:g.33671G>A
NC_000001.10:g.10032156G>A
NP_073624.2:p.Val9Met
missense
V9M
VAL9MET
1p36.2
nicotinamide nucleotide adenylyltransferase 1
NMNAT1
Leber congenital amaurosis 9
Leber Congenital Amaurosis
LCA9
Leber congenital amaurosis (LCA), a severe dystrophy of the retina, typically becomes evident in the first year of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia, and keratoconus. Visual acuity is rarely better than 20/400. A characteristic finding is Franceschetti's oculo-digital sign, comprising eye poking, pressing, and rubbing. The appearance of the fundus is extremely variable. While the retina may initially appear normal, a pigmentary retinopathy reminiscent of retinitis pigmentosa is frequently observed later in childhood. The electroretinogram (ERG) is characteristically "nondetectable" or severely subnormal.
Neonatal/infancy
1-9 / 100 000
20301475
current
Pathogenic
germline
human
not provided
curation
In 3 sibs and 2 cousins from a consanguineous Pakistani pedigree with Leber congenital amaurosis (LCA9; 608553), Falk et al. (2012) identified homozygosity for a 25G-A transition in exon 2 of the NMNAT1 gene, resulting in a val9-to-met (V9M) substitution at a highly conserved residue. The mutation segregated with disease in the pedigree and was not found in 501 controls or in any public databases. Only 1 of the affected individuals had isolated LCA; 3 of the other LCA patients also had congenital deafness, and in those patients as well as in 2 other family members with congenital deafness, homozygosity for a nonsense mutation in the GJB2 gene (W24X; 121011.0003) known to cause deafness (see DFNB1A, 220290) was identified. Additional features in 4 of the LCA patients included global developmental delay and autism; Falk et al. (2012) stated that those presentations likely had a separate genetic etiology from that of LCA and deafness in this pedigree.
22842227
NMNAT1, VAL9MET
VAL9MET
NMNAT1
LEBER CONGENITAL AMAUROSIS 9