| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Skeletal dysplasia v1.112 | TK1 |
chirag patel gene: TK1 was added gene: TK1 was added to Skeletal dysplasia. Sources: Other Mode of inheritance for gene: TK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: TK1 were set to Thoracolaryngopelvic dysplasia, MONDO:0008551 Review for gene: TK1 was set to AMBER Added comment: ESHG 2026 Barnes syndrome (thoraco-laryngo-pelvic dysplasia/TLPD) is a very rare autosomal dominant skeletal dysplasia, clinically characterised by thoracic dystrophy, narrow pelvis and laryngeal stenosis. They report 3 unrelated individuals with TLPD with neonatal hypotonia, thoracic dystrophy with short ribs, subglottic stenosis/tracheal hypoplasia requiring tracheostomy, and narrow pelvis with delayed ossification of pubic rami. Trio WGS identified 2 different rare heterozygous de novo variants (1 x p.Phe29Leu and 2 x p.Lys170del) in TK1 gene. TK1 gene codes for cytosolic thymidine kinase, which phosphorylates thymidine and plays role in DNA synthesis and cell proliferation. Functional studies in lymphoblastoid cell lines suggest a significant reduction of TK1 activity. Further studies are needed to clarify the role of TK1 in bone morphogenesis. Sources: Other |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.106 | PRDM1 |
chirag patel gene: PRDM1 was added gene: PRDM1 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: PRDM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRDM1 were set to 38456586; 37083955 Phenotypes for gene: PRDM1 were set to Split hand-foot malformation MONDO:0016576, PRDM1-related Review for gene: PRDM1 was set to GREEN Added comment: PMID 38456586 (and PMID 37083955) report 3 families with split hand/foot malformation (SHFM) caused by heterozygous PRDM1 variants. The frameshift variant (c.712_713insT) segregated in a multigenerational family (3 affected individuals) with variable penetrance (2 unaffected individuals). The 2 missense variants (p.T524R and p.T819A) were de novo (but the p.T819A variant exceeds population‑frequency thresholds). Zebrafish rescue assays showing loss‑of‑function, as wild‑type human PRDM1 rescues fin defects, whereas each mutant mRNA fails to rescue. Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v1.0 | EED | Gene migrated from ENSG00000074266 to ENSG00000074266 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.443 | CWC27 | Zornitza Stark changed review comment from: Highly variable phenotype characterised by RP and brachydactyly. RP is slowly progressive, with night blindness occurring around 10 years of age (one individual reported with much more severe LCA phenotype). Additional features present in many individuals including frontal bossing, downslanting palpebral fissures, large columella, hypoplastic nares, micrognathia, and large low-set ears. Neurologic features included delays in speech, feeding, and walking, as well as intellectual disability (mild to moderate range). Congenital anomalies affecting heart/kidneys reported. Eight unrelated families reported.; to: Highly variable phenotype characterised by RP and metaphyseal chondrodysplasia, typically brachydactyly. RP is slowly progressive, with night blindness occurring around 10 years of age (one individual reported with much more severe LCA phenotype). Additional features present in many individuals including frontal bossing, downslanting palpebral fissures, large columella, hypoplastic nares, micrognathia, and large low-set ears. Neurologic features included delays in speech, feeding, and walking, as well as intellectual disability (mild to moderate range). Congenital anomalies affecting heart/kidneys reported. Eight unrelated families reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.0 | 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 | FBLIM1 |
Zornitza Stark gene: FBLIM1 was added gene: FBLIM1 was added to Skeletal dysplasia. Sources: NHS GMS Mode of inheritance for gene: FBLIM1 was set to Publications for gene: FBLIM1 were set to 29912021 Phenotypes for gene: FBLIM1 were set to Majeed syndrome (Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia) 609628 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | RASGRP2 |
Zornitza Stark gene: RASGRP2 was added gene: RASGRP2 was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: RASGRP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RASGRP2 were set to 18709451; 24958846 Phenotypes for gene: RASGRP2 were set to Bleeding disorder, platelet-type, 18 615888, also with osteopetrosis like bone abnormalities and neurodevelopmental defects; Bleeding disorder, platelet-type, 18 615888 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | LPIN2 |
Zornitza Stark gene: LPIN2 was added gene: LPIN2 was added to Skeletal dysplasia. Sources: Expert list,NHS GMS,Radboud University Medical Center, Nijmegen,Expert Review Green,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: LPIN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LPIN2 were set to 29912021 Phenotypes for gene: LPIN2 were set to Majeed syndrome (Chronic recurrent multifocal osteomyelitis with congenital dyserythropoietic anemia) 609628 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | FLNA |
Zornitza Stark gene: FLNA was added gene: FLNA was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: FLNA were set to Frontometaphyseal dysplasia 305620; Otopalatodigital syndrome, type II -304120; Osteodysplasty Melnick Needles 309350 XLD; Melnick Needles syndrome 309350; Otopalatodigital syndrome, type II 304120 XLD; Frontometaphyseal dysplasia 305620 XLR; Terminal osseous dysplasia 300244; Otopalatodigital syndrome, type I -311300 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal dysplasia v0.0 | EED |
Zornitza Stark gene: EED was added gene: EED was added to Skeletal dysplasia. Sources: NHS GMS,Literature,Expert Review Green Mode of inheritance for gene: EED was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EED were set to 27868325; 25787343; 28229514; 27193220 Phenotypes for gene: EED were set to Cohen-Gibson syndrome 617561; Cohen-Gibson syndrome 617561 |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||