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| Skeletal dysplasia v0.289 | DDX41 |
Chirag Patel gene: DDX41 was added gene: DDX41 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: DDX41 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DDX41 were set to PMID: 39453476 Phenotypes for gene: DDX41 were set to Bone dysplasia, ichthyosis, and dysmorphism Review for gene: DDX41 was set to RED Added comment: 1 patient with acromesomelic dysplasia (short stature, premature closure of epiphyses of hands/feet), chronic ichthyotic-like skin changes, joint pain, facial dysmorphism, dental crowding, difficulty in swallowing, hyperinsulinism, and absent breast development.. WES identified compound heterozygous DDX41 variants (p.Met155Ile and p.Glu345Lys). Parents confirmed carriers of single variant. DDX41 (DEAD‑box helicase 41) is a member of the largest family of RNA helicases. The DEAD-box RNA helicases regulate all aspects of RNA metabolism. DDX41 acts as a sensor of viral DNA and activates the STING-TBK1-IRF3-type I IFN signaling pathway. Functional analyses of the patient-derived dermal fibroblasts revealed a reduced abundance of DDX41 and abrogated activation of the IFN genes through the STING-type I interferon pathway. Genome-wide transcriptome analyses in the patient's fibroblasts revealed significant gene dysregulation and changes in the RNA splicing events. The patient's fibroblasts also displayed upregulation of periostin mRNA expression. Using an RNA binding protein assay, they identified DDX41 as a novel regulator of periostin expression. Sources: Literature |
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| Skeletal dysplasia v0.238 | IFT74 |
Naomi Baker gene: IFT74 was added gene: IFT74 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: IFT74 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IFT74 were set to PMID:37315079 Phenotypes for gene: IFT74 were set to Jeune syndrome (MONDO:0018770), IFT74-related Review for gene: IFT74 was set to GREEN Added comment: Five individuals from four families reported. A homozygous exon 2 deletion was identified in two families, and splice variants were identified in the other two families (with minigene experiments demonstrating an effect on splicing of the non-canonical/deep intronic splice variants). Authors also characterised three mouse Ift74 alleles, with phenotypes ranging from a severe mid gestational lethal phenotype in the Ift74Tm1d out of frame exon 3 deletion allele, a post-natal lethal phenotype in the Ift74Tm1a exon 2 skip allele, to no detectable phenotype in Ift74Tm1b in frame exon 3 deletion allele. Sources: Literature |
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| Skeletal dysplasia v0.93 | NEPRO |
Zornitza Stark gene: NEPRO was added gene: NEPRO was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: NEPRO was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEPRO were set to 26633546; 29620724; 31250547 Phenotypes for gene: NEPRO were set to Anauxetic dysplasia 3, MIM618853 Review for gene: NEPRO was set to AMBER Added comment: PMIDs 26633546, 29620724: 2 families with the same homozygous missense variant, haplotype analysis confirmed the founder nature of the variant. PMID 31250547: 1 family with homozygous novel missense All 5 affected individuals have severe short stature, brachydactyly, skin laxity, joint hypermobility, and joint dislocations. They also have short metacarpals, broad middle phalanges, and metaphyseal irregularities. No functional studies. Sources: Literature |
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| Skeletal dysplasia v0.45 | MTX2 |
Zornitza Stark gene: MTX2 was added gene: MTX2 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: MTX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MTX2 were set to 32917887 Phenotypes for gene: MTX2 were set to Mandibuloacral dysplasia; lipodystrophy; arterial calcification Review for gene: MTX2 was set to GREEN Added comment: Seven individuals from 5 unrelated families reported with severe progeroid form of MAD with growth retardation, small viscerocranium with mandibular underdevelopment, distal acro-osteolyses, lipodystrophy, altered skin pigmentation, renal focal glomerulosclerosis, and extremely severe hypertension in most cases, eventually associated with disseminated arterial calcification. Loss of MTX2 in patients' primary fibroblasts led to loss of Metaxin-1 (MTX1) and mitochondrial dysfunction, including network fragmentation and oxidative phosphorylation impairment. Furthermore, patients' fibroblasts were resistant to induced apoptosis, leading to increased cell senescence and mitophagy and reduced proliferation. Sources: Literature |
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| 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 |
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| 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 |
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| Skeletal dysplasia v0.0 | SKI |
Zornitza Stark gene: SKI was added gene: SKI was added to Skeletal dysplasia. Sources: NHS GMS,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green Mode of inheritance for gene: SKI was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: SKI were set to Shprintzen-Goldberg syndrome 182212 |
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| Skeletal dysplasia v0.0 | PTDSS1 |
Zornitza Stark gene: PTDSS1 was added gene: PTDSS1 was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: PTDSS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: PTDSS1 were set to Lenz-Majewski hyperostotic dwarfism 151050 |
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| Skeletal dysplasia v0.0 | NEK1 |
Zornitza Stark gene: NEK1 was added gene: NEK1 was added to Skeletal dysplasia. Sources: Emory Genetics Laboratory,NHS GMS,Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: NEK1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: NEK1 were set to Short rib thoracic dysplasia 6 with or without polydactyly - 263520; Short rib-polydactyly syndrome, type IIA, 263520; Short Rib Polydactyly Syndrome; SRPS type 2 (Majewski) |
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| Skeletal dysplasia v0.0 | FBN1 |
Zornitza Stark gene: FBN1 was added gene: FBN1 was added to Skeletal dysplasia. Sources: NHS GMS,Expert Review Green Mode of inheritance for gene: FBN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: FBN1 were set to Stiff skin syndrome 184900; Marfan syndrome 154700; Geleophysic dysplasia 2 614185; Weill-Marchesani syndrome 2, dominant 608328; Acromicric dysplasia 102370 |
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