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| Disorders of sex development v2.11 | TCF12 |
Arina Puzriakova changed review comment from: Comment on list classification: Variants in TCF12 typically cause craniosynostosis, while evidence for an association with Kallmann Syndrome is currently based on a single study, and therefore warrants further investigation. Furthermore, the presence of incomplete penetrance must be considered. Additional cases would help validate the pathogenicity of TCF12 variants in aberrant GnRH axis development. Therefore, rating Amber in anticipation of additional publications/clinical evidence (added to watchlist).; to: Comment on list classification: Variants in TCF12 typically cause craniosynostosis, while evidence for an association with Kallmann Syndrome is currently based on a single study, and therefore warrants further investigation. Furthermore, the presence of incomplete penetrance must be considered. Additional cases would help validate the pathogenicity of TCF12 variants in aberrant GnRH axis development. Therefore, rating Amber in anticipation of additional publications/clinical evidence (added to watchlist). |
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| Disorders of sex development v2.11 | TCF12 | Arina Puzriakova Tag watchlist tag was added to gene: TCF12. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Disorders of sex development v2.11 | TCF12 | Arina Puzriakova Classified gene: TCF12 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Disorders of sex development v2.11 | TCF12 |
Arina Puzriakova Added comment: Comment on list classification: Variants in TCF12 typically cause craniosynostosis, while evidence for an association with Kallmann Syndrome is currently based on a single study, and therefore warrants further investigation. Furthermore, the presence of incomplete penetrance must be considered. Additional cases would help validate the pathogenicity of TCF12 variants in aberrant GnRH axis development. Therefore, rating Amber in anticipation of additional publications/clinical evidence (added to watchlist). |
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| Disorders of sex development v2.11 | TCF12 | Arina Puzriakova Gene: tcf12 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Disorders of sex development v2.10 | TCF12 |
Arina Puzriakova gene: TCF12 was added gene: TCF12 was added to Disorders of sex development. Sources: Literature Mode of inheritance for gene: TCF12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TCF12 were set to 32620954 Phenotypes for gene: TCF12 were set to Kallmann syndrome Review for gene: TCF12 was set to AMBER Added comment: Note monoallelic variants in this gene are a well-established cause of craniosynostosis. -------------------------------------------------------------------------------------------------------------------- - PMID: 32620954 (2020) - 13 unrelated kindreds (11 de novo, 1 AD and 1 AR) comprising 14 affected individuals with an anosmic form of isolated GnRH deficiency (IGD) (Kallman syndrome) due to different LoF variants in TCF12. Clinical manifestation included anosmia and pubertal failure (with reproductive phenotypes such as micropenis, bilateral cryptorchidism, hypospadias). Two unrelated individuals within the cohort additionally exhibited craniosynostosis, and a further two pedigrees had a family history of craniosynostosis (that did not affect the index cases). Multiplex cases typically presented incomplete penetrance. Loss of tcf12 in a mutant zebrafish model perturbed GnRH neuronal patterning, with concomitant expression attenuation of tcf3a/b and stub1 (latter mutated in other syndromic forms of IGD). Furthermore, restored STUB1 expression rescued loss of tcf12 in vivo. Sources: Literature |
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