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<p>Syndromes associating both eyeball and periocular developmental anomalies, combining iris chorioretinal (ocular) coloboma and ptosis, are described in very rare clinical entities such as Baraitser-Winter cerebrofrontofacial syndrome (BWCFF). We report on six individuals from 3 unrelated families presenting with autosomal dominant eye malformations, including ocular coloboma, ptosis and craniofacial features suggesting BWCFF. However, no neurodevelopmental disorders (NDD) as usually observed in this syndrome were detected. Exome sequencing (ES) or genome sequencing (GS) was performed and allowed the identification of 3 novel heterozygous variants in the <i>MYH10</i> gene, encoding the non-muscle myosin heavy chain II B. These 3 likely causative variants occur in the MYH10 tail domain required for myosin filament assembly. The MYH10 protein is mislocalized leading to abnormal actin networks in the patients’ fibroblasts compared to controls. MYH10 dysfunction leads to delayed development of the eye, as well as a muscular phenotype in the zebrafish model. Heterozygous variants in <i>MYH10</i> have been recently reported to be associated with an autosomal dominant NDD with other congenital anomalies, but no patients were reported with the association of ocular coloboma and ptosis as main features. Herein, we report other <i>MYH10</i> variants which cause mainly an ophthalmic phenotype without NDD expanding the phenotype associated with <i>MYH10</i> and representing a differential diagnosis with BWCFF. The reason for the genotype-phenotype variability with either prominent NDD or prominent ocular features will require further investigations.</p>

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Novel MYH10 heterozygous variants associated to a syndrome combining mainly ptosis and ocular coloboma expand the MYH10 related phenotypes

  • 期刊论文

  • 发表日期：

    2025年3月5日

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  • Sophie Scheidecker,
  • Séverine Bär,
  • Ariane Kröll-Hermi,
  • Clarisse Delvallée,
  • Bruno Rinaldi,
  • Anita Korpioja,
  • Véronique Geoffroy,
  • Elise Schaefer,
  • Samira Secula,
  • Catherine Jaeger,
  • Corinne Stoetzel,
  • Olivier Kassel,
  • Uwe Straehle,
  • Aida Bertoli-Avella,
  • Emir Zonic,
  • Jean-Baptiste Lamouche,
  • Xavier Zanlonghi,
  • Christelle Etard,
  • Jean Muller,
  • Elisa Rahikkala,
  • Sylvie Friant,
  • Hélène Dollfus

摘要

Syndromes associating both eyeball and periocular developmental anomalies, combining iris chorioretinal (ocular) coloboma and ptosis, are described in very rare clinical entities such as Baraitser-Winter cerebrofrontofacial syndrome (BWCFF). We report on six individuals from 3 unrelated families presenting with autosomal dominant eye malformations, including ocular coloboma, ptosis and craniofacial features suggesting BWCFF. However, no neurodevelopmental disorders (NDD) as usually observed in this syndrome were detected. Exome sequencing (ES) or genome sequencing (GS) was performed and allowed the identification of 3 novel heterozygous variants in the MYH10 gene, encoding the non-muscle myosin heavy chain II B. These 3 likely causative variants occur in the MYH10 tail domain required for myosin filament assembly. The MYH10 protein is mislocalized leading to abnormal actin networks in the patients’ fibroblasts compared to controls. MYH10 dysfunction leads to delayed development of the eye, as well as a muscular phenotype in the zebrafish model. Heterozygous variants in MYH10 have been recently reported to be associated with an autosomal dominant NDD with other congenital anomalies, but no patients were reported with the association of ocular coloboma and ptosis as main features. Herein, we report other MYH10 variants which cause mainly an ophthalmic phenotype without NDD expanding the phenotype associated with MYH10 and representing a differential diagnosis with BWCFF. The reason for the genotype-phenotype variability with either prominent NDD or prominent ocular features will require further investigations.