Expanding the genetic landscape of oral-facial-digital syndrome with two novel genes
| Autor: | Alanna Strong, Deborah Watson, Hayley Ron, Hakon Hakonarson, Laurie Simone, Elaine H. Zackai, Anthony D. Krentz, Courtney Vaccaro, Jennifer M. Kalish, Helio Pedro |
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| Rok vydání: | 2021 |
| Předmět: |
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Male congenital hereditary and neonatal diseases and abnormalities Genotype Ubiquitin-Protein Ligases Biology oral‐facial‐digital syndrome Exome Sequencing Genetics medicine CEP164 Missense mutation Humans Genetic Predisposition to Disease Genetic Testing Allele Genetics (clinical) Exome sequencing Alleles Genetic Association Studies Polydactyly Cilium Infant Newborn Genetic Variation Infant Nuclear Proteins TOPORS Original Articles Orofaciodigital Syndromes medicine.disease Magnetic Resonance Imaging Neoplasm Proteins Ciliopathy Phenotype ciliopathy Polysyndactyly Mutation Female Original Article |
| Zdroj: | American Journal of Medical Genetics. Part a |
| ISSN: | 1552-4833 |
| Popis: | Oral‐facial‐digital syndromes (OFDS) are a heterogeneous and rare group of Mendelian disorders characterized by developmental abnormalities of the oral cavity, face, and digits caused by dysfunction of the primary cilium, a mechanosensory organelle that exists atop most cell types that facilitates organ patterning and growth. OFDS is inherited both in an X‐linked dominant, X‐linked recessive, and autosomal recessive manner. Importantly, though many of the causal genes for OFDS have been identified, up to 40% of OFD syndromes are of unknown genetic basis. Here we describe three children with classical presentations of OFDS including lingual hamartomas, polydactyly, and characteristic facial features found by exome sequencing to harbor variants in causal genes not previously associated with OFDS. We describe a female with hypothalamic hamartoma, urogenital sinus, polysyndactyly, and multiple lingual hamartomas consistent with OFDVI with biallelic pathogenic variants in CEP164, a gene associated with ciliopathy‐spectrum disease, but never before with OFDS. We additionally describe two unrelated probands with postaxial polydactyly, multiple lingual hamartomas, and dysmorphic features both found to be homozygous for an identical TOPORS missense variant, c.29 C>A; (p.Pro10Gln). Heterozygous TOPORS pathogenic gene variants are associated with autosomal dominant retinitis pigmentosa, but never before with syndromic ciliopathy. Of note, both probands are of Dominican ancestry, suggesting a possible founder allele. |
| Databáze: | OpenAIRE |
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