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| Congenital hypothyroidism v4.1 | SLC16A2 | Adam Gunning changed review comment from: Groeneweg et al., 2025 (PMID: 40420837) describe 8 females with heterozygous SLC16A2 variants; 5 with missense variants, 1 frameshift, and 2 translocations, t(X;19) and t(X;20), that disrupt SLC16A2. Phenotypes included variable neurocognitive impairment, psychiatric/behavioural features, and an appropriate thyroid profile. Compared with asymptomatic carrier, and non-carrier female relatives, affected individuals had lower FT4, higher T3, and lower rT3. Both translocation cases appeared to be as severe as affected males. X-chromosome inactivation studies in patient fibroblasts showed skewed X-inactivation in all 7 evaluated individuals. Functional studies showed that missense variants markedly reduced MCT8-mediated thyroid hormone uptake in vitro, and MCT8-specific T3 uptake was reduced in fibroblasts from 5 of 7 tested patients. This adds to previously reported affected heterozygous females (Frints et al, 2008 PMID: 18398436; Quesada-Espinosa et al, 2021 PMID:34296368; Olivati et al, 2022 PMID: 35782622; Sriram et al, 2024 PMID:38345890).; to: Groeneweg et al., 2025 (PMID: 40420837) describe 8 females with heterozygous SLC16A2 variants; 5 with missense variants, 1 frameshift, and 2 translocations, t(X;19) and t(X;20), that disrupt SLC16A2. Phenotypes included variable neurocognitive impairment, psychiatric/behavioural features, and an appropriate thyroid profile. Compared with asymptomatic carrier, and non-carrier female relatives, affected individuals had lower FT4, higher T3, and lower rT3. Both translocation cases appeared to be as severe as affected males. X-chromosome inactivation studies in patient fibroblasts showed skewed X-inactivation in all 7 evaluated individuals. Functional studies showed that missense variants markedly reduced MCT8-mediated thyroid hormone uptake in vitro, and MCT8-specific T3 uptake was reduced in fibroblasts from 5 of 7 tested patients. This adds to previously reported affected heterozygous females (Frints et al, 2008 PMID: 18398436; Quesada-Espinosa et al, 2021 PMID:34296368; Olivati et al, 2022 PMID: 35782622; Sriram et al, 2024 PMID:38345890). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hypothyroidism v4.1 | SLC16A2 | Adam Gunning reviewed gene: SLC16A2: Rating: GREEN; Mode of pathogenicity: None; Publications: (PMID: 40420837, 18398436, 34296368, 35782622, 38345890); Phenotypes: Allan-Herndon-Dudley syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hypothyroidism v2.5 | SLC16A2 | Arina Puzriakova Phenotypes for gene: SLC16A2 were changed from MENTAL RETARDATION AND MUSCULAR ATROPHY; MCT8 (SLC16A2)-specific thyroid hormone cell transporter deficiency; monocarboxylate transporter 8 (MCT8) deficiency; ALLAN-HERNDON SYNDROME; Monocarboxylate transporter 8 (MCT8) defect; Allan-Herndon-Dudley syndrome; AHDS; MENTAL RETARDATION, X-LINKED, WITH HYPOTONIA; Allan_Herndon_Dudley Syndrome; mental retardation, X-linked, with hypotonia; MONOCARBOXYLATE TRANSPORTER 8 DEFICIENCY; Allan-Herndon-Dudley Syndrome; T3 RESISTANCE; TRIIODOTHYRONINE RESISTANCE; 300523; Allan-Herndon-Dudley syndrome, 300523; ALLAN-HERNDON-DUDLEY SYNDROME to Allan-Herndon-Dudley syndrome, OMIM:300523 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hypothyroidism v1.9 | SLC16A2 | Ellen McDonagh Tag treatable tag was added to gene: SLC16A2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hypothyroidism v1.9 | SLC16A2 | Ellen McDonagh commented on gene: SLC16A2: To expand the scope of this panel, this gene was added and the version changed to 1.8. This gene and information originates from the Hyperthyroidism panel (Version 1.6, code 236). This addition was approved by the Genomics England Clinical Team. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hypothyroidism v1.8 | SLC16A2 |
Ellen McDonagh gene: SLC16A2 was added gene: SLC16A2 was added to Congenital hypothyroidism. Sources: Expert Review Green Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SLC16A2 were set to 24847459 Phenotypes for gene: SLC16A2 were set to MENTAL RETARDATION AND MUSCULAR ATROPHY; MCT8 (SLC16A2)-specific thyroid hormone cell transporter deficiency; monocarboxylate transporter 8 (MCT8) deficiency; ALLAN-HERNDON SYNDROME; Monocarboxylate transporter 8 (MCT8) defect; Allan-Herndon-Dudley syndrome; AHDS; MENTAL RETARDATION, X-LINKED, WITH HYPOTONIA; Allan_Herndon_Dudley Syndrome; mental retardation, X-linked, with hypotonia; MONOCARBOXYLATE TRANSPORTER 8 DEFICIENCY; Allan-Herndon-Dudley Syndrome; T3 RESISTANCE; TRIIODOTHYRONINE RESISTANCE; 300523; Allan-Herndon-Dudley syndrome, 300523; ALLAN-HERNDON-DUDLEY SYNDROME |
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