Expanding the phenotypic and genotypic spectrum of TENM3-related syndromic microphthalmia
Ophthalmic Genetics, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1080/13816810.2026.2673384
- Dergi Adı: Ophthalmic Genetics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO)
- Anahtar Kelimeler: microphthalmia, teneurins, TENM3
- Gazi Üniversitesi Adresli: Evet
Özet
Purpose: To expand the phenotypic and genotypic spectrum of syndromic microphthalmia 15 (MCOPS15; OMIM #615145), a rare disorder caused by biallelic pathogenic variants in teneurin transmembrane protein 3. Methods: We report two affected siblings with syndromic microphthalmia and global developmental delay. Detailed ophthalmological, neurodevelopmental, and systemic clinical evaluation was performed. Exome sequencing was carried out in the elder brother, with variant classification per ACMG 2015 guidelines, followed by Sanger segregation analysis in the younger brother. Results: Both siblings harbored a novel homozygous frameshift variant, c.6417_6420del (p.Thr2140Phefs*7), in TENM3 (NM_001080477.4), classified as likely pathogenic (PVS1, PM2). The elder brother presented with microphthalmia, intellectual disability, choroidal coloboma, nystagmus, nephrolithiasis, and hypospadias; the younger brother showed more pronounced global developmental delay, milder ocular involvement, pes planus, and a double external urethral orifice. Conclusions: These findings expand the known spectrum of TENM3-related microphthalmia. Genitourinary anomalies, not consistently described in prior reports, may represent true phenotypic variability, incomplete evaluation, or selective reporting in series focused on the ocular and neurodevelopmental phenotype.