| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Skeletal dysplasia v1.124 | ATRIP | Zornitza Stark Marked gene: ATRIP as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.124 | ATRIP | Zornitza Stark Gene: atrip has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.124 | ATRIP | Zornitza Stark Classified gene: ATRIP as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.124 | ATRIP | Zornitza Stark Gene: atrip has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.123 | ATRIP |
Zornitza Stark gene: ATRIP was added gene: ATRIP was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: ATRIP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATRIP were set to 40029331 Phenotypes for gene: ATRIP were set to Seckel syndrome, MONDO:0019342, ATRIP-related Review for gene: ATRIP was set to GREEN Added comment: PMID 40029331 reports 3 individuals from three families with biallelic ATRIP splice variants presenting with microcephalic primordial dwarfism and combined immunodeficiency. Affected individuals exhibit severe intrauterine growth restriction, post‑natal short stature, microcephaly and recurrent infections. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.115 | LRRFIP1 |
chirag patel gene: LRRFIP1 was added gene: LRRFIP1 was added to Skeletal dysplasia. Sources: Other deep intronic tags were added to gene: LRRFIP1. Mode of inheritance for gene: LRRFIP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: LRRFIP1 were set to Spondylodysplastic-erosive early-onset scoliosis Review for gene: LRRFIP1 was set to RED Added comment: ESHG 2026 Multiple individuals from 1 large multigenerational family with early-onset scoliosis, with a unique pattern of spondylodysplastic elements and progressive endplate erosion. Penetrance was 100% in the family. Linkage analysis and WGS identified a rare noncoding variant in the regulatory element in intron 1 of the LRRFIP1 gene (c.96+34737C>T). The variant segregated with disease in the family. Short- and long-read RNA sequencing in patient fibroblasts showed altered transcription factor binding and alteration of relative LRRFIP1-isoform expression. Differential gene expression analyses in patient fibroblasts showed alterations in Wnt-signaling during somitogenesis, extracellular matrix organization and TNF-a/NF-kb signaling, partially overlapping with features of common spinal disorders such as Ankylosing Spondylitis. Lrrfip1-knockout mouse had a significantly increased prevalence of kyphoscoliosis. Rare variant enrichment analysis using genome data from UK Biobank participants showed significant enrichment of LRRFIP1-variants in individuals with idiopathic scoliosis. Sources: Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.59 | PRKACA | chirag patel Phenotypes for gene: PRKACA were changed from Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability to Cardioacrofacial dysplasia 1, MONDO:0030876 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.57 | PRKACA |
chirag patel gene: PRKACA was added gene: PRKACA was added to Skeletal dysplasia. Sources: Expert Review Green,Literature Mode of inheritance for gene: PRKACA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: PRKACA were set to 33058759; 31130284 Phenotypes for gene: PRKACA were set to Cardioacrofacial dysplasia 1, MIM# 619142; Postaxial hand polydactyly; Postaxial foot polydactyly; Common atrium; Atrioventricular canal defect; Narrow chest; Abnormality of the teeth; Intellectual disability Penetrance for gene: PRKACA were set to Complete Mode of pathogenicity for gene: PRKACA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.25 | POLR3A |
chirag patel gene: POLR3A was added gene: POLR3A was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: POLR3A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLR3A were set to 30414627, 30450527, 30323018, 21671373, 10607952 Phenotypes for gene: POLR3A were set to Wiedemann-Rautenstrauch syndrome, MONDO:0009910 Review for gene: POLR3A was set to GREEN Added comment: Multiple families reported with biallelic variants in POLR3A and Wiedemann-Rautenstrauch syndrome (WDRTS). This is a rare autosomal recessive neonatal progeroid disorder characterized by intrauterine growth retardation, failure to thrive, short stature, a progeroid appearance, generalized lipoatrophy, various skeletal anomalies, hypotonia, and variable mental impairment. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.0 | ATR | Gene migrated from ENSG00000175054 to ENSG00000175054 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.420 | DLX5 | Zornitza Stark edited their review of gene: DLX5: Added comment: PMID 41760400 adds a new family with a homozygous nonsense DLX5 variant c.97G>T (NM_005221.6) causing autosomal recessive split‑hand/foot malformation type 1D (SHFM1D) accompanied by hypospadias, sensorineural hearing loss and atrial septal defect; Changed publications: 41760400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.405 | ATR | chirag patel Marked gene: ATR as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.405 | ATR | chirag patel Gene: atr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.404 | chirag patel Copied gene ATR from panel Mendeliome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.404 | ATR |
chirag patel gene: ATR was added gene: ATR was added to Skeletal dysplasia. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: ATR was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATR were set to 12640452; 19620979; 30199583; 23111928 Phenotypes for gene: ATR were set to Seckel syndrome 1, MIM# 210600 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.372 | HOXD13_SPD1_GCG |
Bryony Thompson STR: HOXD13_SPD1_GCG was added STR: HOXD13_SPD1_GCG was added to Skeletal dysplasia. Sources: Expert Review Green,Expert list paediatric-onset tags were added to STR: HOXD13_SPD1_GCG. Mode of inheritance for STR: HOXD13_SPD1_GCG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: HOXD13_SPD1_GCG were set to 8817328; 33811808; 33533119 Phenotypes for STR: HOXD13_SPD1_GCG were set to Synpolydactyly 1 MIM#186000 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.371 | HOXA13_HFGS_GCN3 |
Bryony Thompson STR: HOXA13_HFGS_GCN3 was added STR: HOXA13_HFGS_GCN3 was added to Skeletal dysplasia. Sources: Expert Review Green,Expert list paediatric-onset tags were added to STR: HOXA13_HFGS_GCN3. Mode of inheritance for STR: HOXA13_HFGS_GCN3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: HOXA13_HFGS_GCN3 were set to 10839976; 12073020; 33811808 Phenotypes for STR: HOXA13_HFGS_GCN3 were set to Hand-foot-uterus syndrome MIM#140000 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.370 | COMP_MEDPSACH_GAC |
Bryony Thompson STR: COMP_MEDPSACH_GAC was added STR: COMP_MEDPSACH_GAC was added to Skeletal dysplasia. Sources: Expert Review Green,Literature paediatric-onset tags were added to STR: COMP_MEDPSACH_GAC. Mode of inheritance for STR: COMP_MEDPSACH_GAC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for STR: COMP_MEDPSACH_GAC were set to 9887340; 17133256; 21922596 Phenotypes for STR: COMP_MEDPSACH_GAC were set to Epiphyseal dysplasia, multiple, 1 MIM#132400; Pseudoachondroplasia MIM#177170 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.365 | ISCA-37418-Loss | Zornitza Stark Phenotypes for Region: ISCA-37418-Loss were changed from Potocki-Lupski syndrome; Smith-Magenis syndrome; moderate intellectual disability, delayed speech and language skills, distinctive facial features, sleep disturbances, and behavioral problems; 182290; Structural cardiovascular anomalies (dilated aortic root, bicommissural aortic valve, atrial/ventricular and septal defects) and sleep disturbance; hypotonia, failure to thrive, mental retardation, pervasive developmental disorders, congenital anomalies; Dental abnormalities; hypotonia, poor feeding, failure to thrive, developmental delay particularly cognitive and language deficity, mild-moderate intellectual deficit, and neuropsychiatric disorders to Smith-Magenis syndrome, MIM#182290 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.288 | BMP5 | Zornitza Stark Phenotypes for gene: BMP5 were changed from Skeletal dysostosis and atrioventricular septal defect to Skeletal dysplasia, MONDO:0018230, BMP5-related; Skeletal dysostosis and atrioventricular septal defect | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.287 | BMP5 |
chirag patel changed review comment from: 1 patient with skeletal dysostosis, atrioventricular septal defect, hypermobility, laryngo-tracheo-bronchomalacia and dysmorphic features (malar hypoplasia, short palpebral fissures, short nose, low nasal bridge, anteverted nares, long philtrum, small ears with abnormally folded antihelix). Skeletal survey showed mild thoracolumbar scoliosis, four sacral segments, absent ossification of the inferior pubic rami, and patellar aplasia. Trio WGS identified compound heterozygous loss of function variants in BMP5 (c.88_89del, p.(Gly30Argfs*11) and c.1104+2del, p.(?). Abnormal splicing was proven on the suspected splice variant using maternal fibroblasts. BMP5 expression is confined to specific parts of the skeleton and cartilage in mice and is tightly regulated by different enhancers. Previous studies of chicken embryonic heart development showed BMP5 expression in the endoderm underlying the precardiac mesoderm, the myocardium of the atrioventricular canal and outflow tract regions. Other bone morphogenetic proteins are linked to several genetic skeletal disorders. Sources: Literature; to: 1 patient with skeletal dysostosis, atrioventricular septal defect, hypermobility, laryngo-tracheo-bronchomalacia and dysmorphic features (malar hypoplasia, short palpebral fissures, short nose, low nasal bridge, anteverted nares, long philtrum, small ears with abnormally folded antihelix). Skeletal survey showed mild thoracolumbar scoliosis, four sacral segments, absent ossification of the inferior pubic rami, and patellar aplasia. Trio WGS identified compound heterozygous loss of function variants in BMP5 (c.88_89del, p.(Gly30Argfs*11) and c.1104+2del, p.(?). Abnormal splicing was proven on the suspected splice variant using maternal fibroblasts. BMP5 expression is confined to specific parts of the skeleton and cartilage in mice and is tightly regulated by different enhancers. Previous studies of chicken embryonic heart development showed BMP5 expression in the endoderm underlying the precardiac mesoderm, the myocardium of the atrioventricular canal and outflow tract regions. Other bone morphogenetic proteins are linked to several genetic skeletal disorders. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.287 | BMP5 |
chirag patel gene: BMP5 was added gene: BMP5 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: BMP5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BMP5 were set to PMID: 39239663 Phenotypes for gene: BMP5 were set to Skeletal dysostosis and atrioventricular septal defect Review for gene: BMP5 was set to RED Added comment: 1 patient with skeletal dysostosis, atrioventricular septal defect, hypermobility, laryngo-tracheo-bronchomalacia and dysmorphic features (malar hypoplasia, short palpebral fissures, short nose, low nasal bridge, anteverted nares, long philtrum, small ears with abnormally folded antihelix). Skeletal survey showed mild thoracolumbar scoliosis, four sacral segments, absent ossification of the inferior pubic rami, and patellar aplasia. Trio WGS identified compound heterozygous loss of function variants in BMP5 (c.88_89del, p.(Gly30Argfs*11) and c.1104+2del, p.(?). Abnormal splicing was proven on the suspected splice variant using maternal fibroblasts. BMP5 expression is confined to specific parts of the skeleton and cartilage in mice and is tightly regulated by different enhancers. Previous studies of chicken embryonic heart development showed BMP5 expression in the endoderm underlying the precardiac mesoderm, the myocardium of the atrioventricular canal and outflow tract regions. Other bone morphogenetic proteins are linked to several genetic skeletal disorders. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.109 | GSC | Zornitza Stark Phenotypes for gene: GSC were changed from Foundation Trust) Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities 602471; Foundation Trust) Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities 602471 to Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.107 | GSC | Zornitza Stark reviewed gene: GSC: Rating: GREEN; Mode of pathogenicity: None; Publications: 24290375; Phenotypes: Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities, MIM# 602471; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.70 | FBLN1 |
Zornitza Stark changed review comment from: Single association to disease published in literature - reciprocal translocation region t(12;22)(p11.2;q13.3) found in the family. The breakpoint was located in the intron between the last 2 exons of the FBLN1-D splice variant isoform (exons 19-20). Additional pathogenic missense in ClinVar, but a research finding and inherited; to: Single association of mono-allelic variants to disease published in literature - reciprocal translocation region t(12;22)(p11.2;q13.3) found in the family. The breakpoint was located in the intron between the last 2 exons of the FBLN1-D splice variant isoform (exons 19-20). Additional pathogenic missense in ClinVar, but a research finding and inherited. Single report of homozygous missense in a family with syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | ISCA-37418-Loss |
Zornitza Stark Region: ISCA-37418-Loss was added Region: ISCA-37418-Loss was added to Skeletal dysplasia. Sources: NHS GMS,ClinGen,Expert Review Green Mode of inheritance for Region: ISCA-37418-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for Region: ISCA-37418-Loss were set to Potocki-Lupski syndrome; Smith-Magenis syndrome; moderate intellectual disability, delayed speech and language skills, distinctive facial features, sleep disturbances, and behavioral problems; 182290; Structural cardiovascular anomalies (dilated aortic root, bicommissural aortic valve, atrial/ventricular and septal defects) and sleep disturbance; hypotonia, failure to thrive, mental retardation, pervasive developmental disorders, congenital anomalies; Dental abnormalities; hypotonia, poor feeding, failure to thrive, developmental delay particularly cognitive and language deficity, mild-moderate intellectual deficit, and neuropsychiatric disorders |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | OAT |
Zornitza Stark gene: OAT was added gene: OAT was added to Skeletal dysplasia. Sources: Expert Review Red,NHS GMS Mode of inheritance for gene: OAT was set to Phenotypes for gene: OAT were set to Gyrate atrophy of choroid and retina with or without ornithinemia 258870 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | TRPV4 |
Zornitza Stark gene: TRPV4 was added gene: TRPV4 was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: TRPV4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: TRPV4 were set to Digital arthropathy-brachydactyly, familial 606835; Parastremmatic dwarfism 168400; Scapuloperoneal spinal muscular atrophy 181405; SED, Maroteaux type 184095; Brachyolmia type 3 113500; Hereditary motor and sensory neuropathy, type IIc 606071; Spinal muscular atrophy, distal, congenital nonprogressive 600175; Metatropic dysplasia 156530; Spondylometaphyseal dysplasia, Kozlowski type 184252 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | NBAS |
Zornitza Stark gene: NBAS was added gene: NBAS was added to Skeletal dysplasia. Sources: Radboud University Medical Center, Nijmegen,Expert Review Green Mode of inheritance for gene: NBAS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NBAS were set to 27789416 Phenotypes for gene: NBAS were set to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, 614800 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | GSC |
Zornitza Stark gene: GSC was added gene: GSC was added to Skeletal dysplasia. Sources: NHS GMS,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green Mode of inheritance for gene: GSC was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GSC were set to Foundation Trust) Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities 602471; Foundation Trust) Short stature, auditory canal atresia, mandibular hypoplasia, skeletal abnormalities 602471 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | ATP7A |
Zornitza Stark gene: ATP7A was added gene: ATP7A was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,Expert list,NHS GMS,Radboud University Medical Center, Nijmegen,Expert Review Green,UKGTN Mode of inheritance for gene: ATP7A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ATP7A were set to Spinal muscular atrophy, distal, 300489; Menkes disease 309400; Occipital horn syndrome 304150 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||