論文 - 詳細
| RRC ID | 62620 |
|---|---|
| 著者 | Patel R, Singh SK, Bhattacharya V, Ali A. |
| タイトル | Novel GLI3 pathogenic variants in complex pre- and postaxial polysyndactyly and Greig cephalopolysyndactyly syndrome. |
| ジャーナル | Am J Med Genet A |
| Abstract |
Polydactyly is a limb malformation and can occur as nonsyndromic polydactyly, syndromic polydactyly, or along with other limb defects. A few genes have been identified that cause various forms of syndromic and nonsyndromic polydactyly, of which GLI3 has been extensively explored. In the present study, GLI3 gene was screened by direct resequencing in 15 polydactyly cases with or without other anomalies. GLI3 screening revealed two novel pathogenic variants, NM_000168.6:c.3414delC [p.(H1138Qfs*68)] and NM_000168.6:c.1862C>T [p.(P621L)], found in two unrelated cases of familial complex pre- and postaxial polysyndactyly and sporadic Greig cephalopolysyndactyly syndrome (GCPS), respectively. The first pathogenic GLI3 variant, NM_000168.6:c.3414delC, causes premature protein truncation at the C-terminal domain of GLI3. Alternatively, the second pathogenic variant, NM_000168.6:c.1862C>T, lies in the DNA binding domain of GLI3 protein and may affect its hydrophobic interaction with DNA. Both pathogenic GLI3 variants had reduced transcriptional activity in HEK293 cells that likely had led to haploinsufficiency and, consequently, the clinical phenotypes. Overall, the present study reports a novel familial case of complex pre- and postaxial polysyndactyly and the underlying novel pathogenic GLI3 variant expanding the clinical criteria for GLI3 mutational spectrum to complex pre- and postaxial polysyndactyly. Furthermore, this study also reports a novel GLI3 pathogenic variant linked to GCPS, highlighting the known genotype-phenotype correlation. |
| 巻・号 | 185(1) |
| ページ | 97-104 |
| 公開日 | 2021-1-1 |
| DOI | 10.1002/ajmg.a.61919 |
| PMID | 33058447 |
| MeSH | Acrocephalosyndactylia / diagnosis Acrocephalosyndactylia / genetics* Acrocephalosyndactylia / pathology Adolescent Child Female Genetic Association Studies Genetic Predisposition to Disease* Humans Male Mutation / genetics Nerve Tissue Proteins / genetics* Phenotype Polymorphism, Single Nucleotide Syndactyly / diagnosis Syndactyly / genetics* Syndactyly / pathology Young Adult Zinc Finger Protein Gli3 / genetics* |
| IF | 2.125 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pGL4-phGLI1 (RDB07902) pcDNA3.1-His-hGLI3 (RDB08066) |