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| Skeletal dysplasia v10.17 | POLR1D |
Ida Ertmanska changed review comment from: PMID: 24603435 Schaefer et al., 2014 Report of 2 families. Seq method: direct sequencing of TCOF1, POLR1D, and POLR1C. F1 - proband is a young girl born to distant cousins from Turkey; she had hearing loss, microretrognathia, malar hypoplasia, right-ear dysplasia, and downslanting palpebral fissures. Normal motor and cognitive development. She was hom for POLR1D c.163C>G, p.Leu55Val variant - 2 alleles reported in gnomAD v4.1.2, no hmz. Parents and sister were unaffected and het for the same variant. F2 - 3 affected children hom for POLR1D c.163C>G, p.Leu55Val variant, born to first cousin parents from Turkey (same region as F1). Phenotype: hearing loss, malar hypoplasia, retrognathism. Parents were het for p.Leu55Val and unaffected. Haplotype analysis revealed both families had different microsatellite markers around POLR1D - evidence against a founder mutation. PMID: 25790162 Vincent et al., 2015 Cohort of 146 patients with Treacher Collins Syndrome, mostly of French ancestry. 92 patients had a variant in TCOF1, 9 in POLR1D, and none in POLR1C. Seq method: non-NGS sequencing of TCOF1, POLR1D, POLR1C, and EFTUD2 using Sanger seq, arrays, liquid chromatography. All patients with POLR1D presented with mandibular hypoplasia (7/7) and deafness (5/5 assessed), but not with microcephaly, cardiac or renal malformations, anomaly of the limbs, or choanal atresia. One of the probands (P96) was homozygous for the c.163C>G, p.Leu55Val variant in POLR1D. HOWEVER Suppl Table S1 lists this proband as 'previously reported' - most likely overlapping a proband from PMID: 24603435. PMID: 42706666 Nevondwe et al., 2026 Report of a South African proband (FRASC28, 7yo male) with Treacher Collins Syndrome and a homozygous POLR1D variant NM_015972.4:c.261delA, (p.Gly88AlafsTer13). Variant not present in gnomAD 4.1.2. Individual presented with malar flattening, mandibular hypoplasia, low‐set ears, ear tags, hearing loss, undescended testes. Parental segregation analysis was not performed, but apparently they were unaffected. Seq method: custom NGS gene panel including TCOF1, POLR1C, and POLR1D genes.; to: PMID: 24603435 Schaefer et al., 2014 Report of 2 families. Seq method: direct sequencing of TCOF1, POLR1D, and POLR1C. F1 - proband is a young girl born to distant cousins from Turkey; she had hearing loss, microretrognathia, malar hypoplasia, right-ear dysplasia, and downslanting palpebral fissures. Normal motor and cognitive development. She was hom for POLR1D c.163C>G, p.Leu55Val variant - 2 alleles reported in gnomAD v4.1.2, no hmz. Parents and sister were unaffected and het for the same variant. F2 - 3 affected children hom for POLR1D c.163C>G, p.Leu55Val variant, born to first cousin parents from Turkey (same region as F1). Phenotype: hearing loss, malar hypoplasia, retrognathism. Parents were het for p.Leu55Val and unaffected. Haplotype analysis revealed both families had different microsatellite markers around POLR1D - evidence against a founder mutation. PMID: 25790162 Vincent et al., 2015 Cohort of 146 patients with Treacher Collins Syndrome, mostly of French ancestry. 92 patients had a variant in TCOF1, 9 in POLR1D, and none in POLR1C. All patients with POLR1D presented with mandibular hypoplasia (7/7) and deafness (5/5 assessed), but not with microcephaly, cardiac or renal malformations, anomaly of the limbs, or choanal atresia. One of the probands was homozygous for the c.163C>G, p.Leu55Val variant in POLR1D. Seq method: non-NGS sequencing of TCOF1, POLR1D, POLR1C, and EFTUD2 using Sanger seq, arrays, liquid chromatography. PMID: 42706666 Nevondwe et al., 2026 Report of a South African proband (FRASC28, 7yo male) with Treacher Collins Syndrome and a homozygous POLR1D variant NM_015972.4:c.261delA, (p.Gly88AlafsTer13). Variant not present in gnomAD 4.1.2. Individual presented with malar flattening, mandibular hypoplasia, low‐set ears, ear tags, hearing loss, undescended testes. Parental segregation analysis was not performed, but apparently they were unaffected. Seq method: custom NGS gene panel including TCOF1, POLR1C, and POLR1D genes. FUNCTIONAL: PMID: 27448281 - Watt et al., 2016 - zebrafish Polr1c-/- and polr1d-/- mutant embryos had smaller eyes than WT fish, disrupted midbrain-hindbrain boundary and necrotic cranial tissue at 24 hpf. At 3 dpf, polr1c-/- and polr1d-/- mutants showed smaller heads, microphthalmia, and hyploplastic jaws. Alcian blue staining revealed cartilage is hypoplastic in the knockout fish. POLR1D is associated with AD, AR Treacher Collins syndrome 2, MIM:613717 (OMIM accessed 12th Oct 2026). The assocation between AD Treacher Collins syndrome 2 and POLR1D was classified as Definitive in ClinGen (12/15/2022, Craniofacial Malformations GCEP). |
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| Skeletal dysplasia v10.17 | POLR1D |
Ida Ertmanska changed review comment from: PMID: 24603435 Schaefer et al., 2014 Report of 2 families. Seq method: direct sequencing of TCOF1, POLR1D, and POLR1C. F1 - proband is a young girl born to distant cousins from Turkey; she had hearing loss, microretrognathia, malar hypoplasia, right-ear dysplasia, and downslanting palpebral fissures. Normal motor and cognitive development. She was hom for POLR1D c.163C>G, p.Leu55Val variant - 2 alleles reported in gnomAD v4.1.2, no hmz. Parents and sister were unaffected and het for the same variant. F2 - 3 affected children hom for POLR1D c.163C>G, p.Leu55Val variant, born to first cousin parents from Turkey (same region as F1). Phenotype: hearing loss, malar hypoplasia, retrognathism. Parents were het for p.Leu55Val and unaffected. Haplotype analysis revealed both families had different microsatellite markers around POLR1D - evidence against a founder mutation. PMID: 25790162 Vincent et al., 2015 Cohort of 146 patients with Treacher Collins Syndrome, mostly of French ancestry. 92 patients had a variant in TCOF1, 9 in POLR1D, and none in POLR1C. All patients with POLR1D presented with mandibular hypoplasia (7/7) and deafness (5/5 assessed), but not with microcephaly, cardiac or renal malformations, anomaly of the limbs, or choanal atresia. One of the probands was homozygous for the c.163C>G, p.Leu55Val variant in POLR1D. Seq method: non-NGS sequencing of TCOF1, POLR1D, POLR1C, and EFTUD2 using Sanger seq, arrays, liquid chromatography. PMID: 42706666 Nevondwe et al., 2026 Report of a South African proband (FRASC28, 7yo male) with Treacher Collins Syndrome and a homozygous POLR1D variant NM_015972.4:c.261delA, (p.Gly88AlafsTer13). Variant not present in gnomAD 4.1.2. Individual presented with malar flattening, mandibular hypoplasia, low‐set ears, ear tags, hearing loss, undescended testes. Parental segregation analysis was not performed, but apparently they were unaffected. Seq method: custom NGS gene panel including TCOF1, POLR1C, and POLR1D genes.; to: PMID: 24603435 Schaefer et al., 2014 Report of 2 families. Seq method: direct sequencing of TCOF1, POLR1D, and POLR1C. F1 - proband is a young girl born to distant cousins from Turkey; she had hearing loss, microretrognathia, malar hypoplasia, right-ear dysplasia, and downslanting palpebral fissures. Normal motor and cognitive development. She was hom for POLR1D c.163C>G, p.Leu55Val variant - 2 alleles reported in gnomAD v4.1.2, no hmz. Parents and sister were unaffected and het for the same variant. F2 - 3 affected children hom for POLR1D c.163C>G, p.Leu55Val variant, born to first cousin parents from Turkey (same region as F1). Phenotype: hearing loss, malar hypoplasia, retrognathism. Parents were het for p.Leu55Val and unaffected. Haplotype analysis revealed both families had different microsatellite markers around POLR1D - evidence against a founder mutation. PMID: 25790162 Vincent et al., 2015 Cohort of 146 patients with Treacher Collins Syndrome, mostly of French ancestry. 92 patients had a variant in TCOF1, 9 in POLR1D, and none in POLR1C. Seq method: non-NGS sequencing of TCOF1, POLR1D, POLR1C, and EFTUD2 using Sanger seq, arrays, liquid chromatography. All patients with POLR1D presented with mandibular hypoplasia (7/7) and deafness (5/5 assessed), but not with microcephaly, cardiac or renal malformations, anomaly of the limbs, or choanal atresia. One of the probands (P96) was homozygous for the c.163C>G, p.Leu55Val variant in POLR1D. HOWEVER Suppl Table S1 lists this proband as 'previously reported' - most likely overlapping a proband from PMID: 24603435. PMID: 42706666 Nevondwe et al., 2026 Report of a South African proband (FRASC28, 7yo male) with Treacher Collins Syndrome and a homozygous POLR1D variant NM_015972.4:c.261delA, (p.Gly88AlafsTer13). Variant not present in gnomAD 4.1.2. Individual presented with malar flattening, mandibular hypoplasia, low‐set ears, ear tags, hearing loss, undescended testes. Parental segregation analysis was not performed, but apparently they were unaffected. Seq method: custom NGS gene panel including TCOF1, POLR1C, and POLR1D genes. |
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| Skeletal dysplasia v10.17 | POLR1D |
Ida Ertmanska changed review comment from: PMID: 24603435 Schaefer et al., 2014 Proband hom for POLR1D c.163C>G, p.Leu55Val variant - 2 alleles reported in gnomAD v4.1.2, no hmz. PMID: 25790162 Vincent et al., 2015 Cohort of 146 patients with Treacher Collins Syndrome, mostly of French ancestry. 92 patients had a variant in TCOF1, 9 in POLR1D, and none in POLR1C. All patients with POLR1D presented with mandibular hypoplasia (7/7) and deafness (5/5 assessed), but not with microcephaly, cardiac or renal malformations, anomaly of the limbs, or choanal atresia. One of the probands was homozygous for the c.163C>G, p.Leu55Val variant in POLR1D. Seq method: non-NGS sequencing of TCOF1, POLR1D, POLR1C, and EFTUD2 using Sanger seq, arrays, liquid chromatography. PMID: 42706666 Nevondwe et al., 2026 Report of a South African proband (FRASC28, 7yo male) with Treacher Collins Syndrome and a homozygous POLR1D variant NM_015972.4:c.261delA, (p.Gly88AlafsTer13). Variant not present in gnomAD 4.1.2. Individual presented with malar flattening, mandibular hypoplasia, low‐set ears, ear tags, hearing loss, undescended testes. Parental segregation analysis was not performed, but apparently they were unaffected. Seq method: custom NGS gene panel including TCOF1, POLR1C, and POLR1D genes.; to: PMID: 24603435 Schaefer et al., 2014 Report of 2 families. Seq method: direct sequencing of TCOF1, POLR1D, and POLR1C. F1 - proband is a young girl born to distant cousins from Turkey; she had hearing loss, microretrognathia, malar hypoplasia, right-ear dysplasia, and downslanting palpebral fissures. Normal motor and cognitive development. She was hom for POLR1D c.163C>G, p.Leu55Val variant - 2 alleles reported in gnomAD v4.1.2, no hmz. Parents and sister were unaffected and het for the same variant. F2 - 3 affected children hom for POLR1D c.163C>G, p.Leu55Val variant, born to first cousin parents from Turkey (same region as F1). Phenotype: hearing loss, malar hypoplasia, retrognathism. Parents were het for p.Leu55Val and unaffected. Haplotype analysis revealed both families had different microsatellite markers around POLR1D - evidence against a founder mutation. PMID: 25790162 Vincent et al., 2015 Cohort of 146 patients with Treacher Collins Syndrome, mostly of French ancestry. 92 patients had a variant in TCOF1, 9 in POLR1D, and none in POLR1C. All patients with POLR1D presented with mandibular hypoplasia (7/7) and deafness (5/5 assessed), but not with microcephaly, cardiac or renal malformations, anomaly of the limbs, or choanal atresia. One of the probands was homozygous for the c.163C>G, p.Leu55Val variant in POLR1D. Seq method: non-NGS sequencing of TCOF1, POLR1D, POLR1C, and EFTUD2 using Sanger seq, arrays, liquid chromatography. PMID: 42706666 Nevondwe et al., 2026 Report of a South African proband (FRASC28, 7yo male) with Treacher Collins Syndrome and a homozygous POLR1D variant NM_015972.4:c.261delA, (p.Gly88AlafsTer13). Variant not present in gnomAD 4.1.2. Individual presented with malar flattening, mandibular hypoplasia, low‐set ears, ear tags, hearing loss, undescended testes. Parental segregation analysis was not performed, but apparently they were unaffected. Seq method: custom NGS gene panel including TCOF1, POLR1C, and POLR1D genes. |
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| Skeletal dysplasia v10.17 | POLR1D |
Ida Ertmanska changed review comment from: PMID: 24603435 Schaefer et al., 2014 Proband hom for POLR1D c.163C>G, p.Leu55Val variant. PMID: 25790162 Vincent et al., 2015 Cohort of 146 patients with Treacher Collins Syndrome, mostly of French ancestry. 92 patients had a variant in TCOF1, 9 in POLR1D, and none in POLR1C. All patients with POLR1D presented with mandibular hypoplasia (7/7) and deafness (5/5 assessed), but not with microcephaly, cardiac or renal malformations, anomaly of the limbs, or choanal atresia. One of the probands was homozygous for the c.163C>G, p.Leu55Val variant in POLR1D. Seq method: non-NGS sequencing of TCOF1, POLR1D, POLR1C, and EFTUD2 using Sanger seq, arrays, liquid chromatography. PMID: 42706666 Nevondwe et al., 2026 Report of a South African proband (FRASC28, 7yo male) with Treacher Collins Syndrome and a homozygous POLR1D variant NM_015972.4:c.261delA, (p. Gly88AlafsTer13). He presented with malar flattening, mandibular hypoplasia, low‐set ears, ear tags, hearing loss, undescended testes. Parental segregation analysis was not performed, but apparently they were unaffected. Seq method: custom NGS gene panel including TCOF1, POLR1C, and POLR1D genes.; to: PMID: 24603435 Schaefer et al., 2014 Proband hom for POLR1D c.163C>G, p.Leu55Val variant - 2 alleles reported in gnomAD v4.1.2, no hmz. PMID: 25790162 Vincent et al., 2015 Cohort of 146 patients with Treacher Collins Syndrome, mostly of French ancestry. 92 patients had a variant in TCOF1, 9 in POLR1D, and none in POLR1C. All patients with POLR1D presented with mandibular hypoplasia (7/7) and deafness (5/5 assessed), but not with microcephaly, cardiac or renal malformations, anomaly of the limbs, or choanal atresia. One of the probands was homozygous for the c.163C>G, p.Leu55Val variant in POLR1D. Seq method: non-NGS sequencing of TCOF1, POLR1D, POLR1C, and EFTUD2 using Sanger seq, arrays, liquid chromatography. PMID: 42706666 Nevondwe et al., 2026 Report of a South African proband (FRASC28, 7yo male) with Treacher Collins Syndrome and a homozygous POLR1D variant NM_015972.4:c.261delA, (p.Gly88AlafsTer13). Variant not present in gnomAD 4.1.2. Individual presented with malar flattening, mandibular hypoplasia, low‐set ears, ear tags, hearing loss, undescended testes. Parental segregation analysis was not performed, but apparently they were unaffected. Seq method: custom NGS gene panel including TCOF1, POLR1C, and POLR1D genes. |
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| Skeletal dysplasia v10.17 | POLR1D |
Ida Ertmanska changed review comment from: PMID: 24603435 Schaefer et al., 2014 Proband hom for POLR1D c.163C>G, p.Leu55Val variant. PMID: 25790162 Vincent et al., 2015 Cohort of 146 patients with Treacher Collins Syndrome. 92 patients had a variant in TCOF1, 9 in POLR1D, and none in POLR1C. All patients with POLR1D presented with mandibular hypoplasia (7/7) and deafness (5/5 assessed), but not with microcephaly, cardiac or renal malformations, anomaly of the limbs, or choanal atresia. One of the probands was homozygous for the c.163C>G, p.Leu55Val variant in POLR1D. Seq method: non-NGS sequencing of TCOF1, POLR1D, POLR1C, and EFTUD2 using Sanger seq, arrays, liquid chromatography. PMID: 42706666 Nevondwe et al., 2026 Report of a South African proband (FRASC28, 7yo male) with Treacher Collins Syndrome and a homozygous POLR1D variant NM_015972.4:c.261delA, (p. Gly88AlafsTer13). He presented with malar flattening, mandibular hypoplasia, low‐set ears, ear tags, hearing loss, undescended testes. Parental segregation analysis was not performed, but apparently they were unaffected. Seq method: custom NGS gene panel including TCOF1, POLR1C, and POLR1D genes.; to: PMID: 24603435 Schaefer et al., 2014 Proband hom for POLR1D c.163C>G, p.Leu55Val variant. PMID: 25790162 Vincent et al., 2015 Cohort of 146 patients with Treacher Collins Syndrome, mostly of French ancestry. 92 patients had a variant in TCOF1, 9 in POLR1D, and none in POLR1C. All patients with POLR1D presented with mandibular hypoplasia (7/7) and deafness (5/5 assessed), but not with microcephaly, cardiac or renal malformations, anomaly of the limbs, or choanal atresia. One of the probands was homozygous for the c.163C>G, p.Leu55Val variant in POLR1D. Seq method: non-NGS sequencing of TCOF1, POLR1D, POLR1C, and EFTUD2 using Sanger seq, arrays, liquid chromatography. PMID: 42706666 Nevondwe et al., 2026 Report of a South African proband (FRASC28, 7yo male) with Treacher Collins Syndrome and a homozygous POLR1D variant NM_015972.4:c.261delA, (p. Gly88AlafsTer13). He presented with malar flattening, mandibular hypoplasia, low‐set ears, ear tags, hearing loss, undescended testes. Parental segregation analysis was not performed, but apparently they were unaffected. Seq method: custom NGS gene panel including TCOF1, POLR1C, and POLR1D genes. |
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| Skeletal dysplasia v1.153 | POLR1C | Eleanor Williams Added phenotypes Treacher Collins syndrome 3 248390 for gene: POLR1C | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.147 | POLR1C | Tracy Lester reviewed gene: POLR1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Treacher Collins syndrome 3 248390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.146 | POLR1C | Eleanor Williams reviewed gene: POLR1C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.145 | POLR1C |
Eleanor Williams Source NHS GMS was added to POLR1C. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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