Exclusion of LCA5 locus in a consanguineous Turkish family with macular coloboma-type LCA

Özgül, Rıza Köksal; Bozkurt, Banu; Kıratlı, Hayyam; Öğüş, Ay

doi:10.1038/sj.eye.6702024

Cited by 7 publications

(1 citation statement)

References 17 publications

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“…The clinical manifestations of our patient correlated strongly with those of reported SHILCA cases, including ocular, nervous and skeletal affectations. The retinal involvement was almost identical, with mild optic disc pallor, marked attenuation of retinal vessels and characteristic macular colobomatous atrophy, as already described in other LCA patients [22]. However, the severity of the pathology appeared to be milder for some traits, as was the case regarding the mild sensorineural hearing loss.…”

Section: Discussionsupporting

confidence: 77%

New Insights on the Genetic Basis Underlying SHILCA Syndrome: Characterization of the NMNAT1 Pathological Alterations Due to Compound Heterozygous Mutations and Identification of a Novel Alternative Isoform

Abad-Morales

Wert

Gómez

et al. 2021

IJMS

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This study aims to genetically characterize a two-year-old patient suffering from multiple systemic abnormalities, including skeletal, nervous and developmental involvements and Leber congenital amaurosis (LCA). Genetic screening by next-generation sequencing identified two heterozygous pathogenic variants in nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) as the molecular cause of the disease: c.439+5G>T and c.299+526_*968dup.This splice variant has never been reported to date, whereas pathogenic duplication has recently been associated with cases displaying an autosomal recessive disorder that includes a severe form of spondylo-epiphyseal dysplasia, sensorineural hearing loss, intellectual disability and LCA (SHILCA), as well as some brain anomalies. Our patient presented clinical manifestations which correlated strongly with this reported syndrome. To further study the possible transcriptional alterations resulting from these mutations, mRNA expression assays were performed in the patient and her father. The obtained results detected aberrant alternative transcripts and unbalanced levels of expression, consistent with severe systemic involvement. Moreover, these analyses also detected a novel NMNAT1 isoform, which is variably expressed in healthy human tissues. Altogether, these findings represent new evidence of the correlation of NMNAT1 and SHILCA syndrome, and provide additional insights into the healthy and pathogenic expression of this gene.

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Section: Discussionsupporting

confidence: 77%