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NAA10 – Lenz microphthalmia syndrome

Lenz microphthalmia syndrome (LMS) is a genetically heterogeneous X-linked disorder characterized by microphthalmia/anophthalmia, skeletal anomalies, genitourinary malformations, intellectual disability, and seizure (PMID:24431331). In a single kindred, exome sequencing of three affected brothers identified a hemizygous splice donor variant c.471+2T>A in NAA10 that co-segregated with the phenotype in all three males and was absent in controls ([PMID:24431331]).

Patient fibroblasts exhibited aberrant NAA10 transcripts with loss of full-length protein and reduced proliferation. Expression array analyses showed dysregulation of genes implicated in anophthalmia syndromes (e.g., BMP4, STRA6) and retinol uptake assays confirmed decreased retinol uptake, implicating disruption of the retinoic acid signalling pathway as the pathogenic mechanism ([PMID:24431331]).

References

  • Journal of medical genetics • 2014 • A splice donor mutation in NAA10 results in the dysregulation of the retinoic acid signalling pathway and causes Lenz microphthalmia syndrome PMID:24431331

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

One kindred with three hemizygous male probands, X-linked recessive inheritance and no additional reports

Genetic Evidence

Moderate

Single family with three affected brothers and co-segregation of c.471+2T>A variant in three meioses ([PMID:24431331])

Functional Evidence

Moderate

Aberrant splicing, loss of full-length NAA10 protein, cell proliferation defects, RA pathway dysregulation and decreased retinol uptake in patient fibroblasts ([PMID:24431331])