| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Pulmonary Fibrosis_Interstitial Lung Disease v0.52 | ACD | Bryony Thompson Marked gene: ACD as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.52 | ACD | Bryony Thompson Gene: acd has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.52 | ACD | Bryony Thompson Classified gene: ACD as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.52 | ACD | Bryony Thompson Gene: acd has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pulmonary Fibrosis_Interstitial Lung Disease v0.51 | ACD |
Bryony Thompson gene: ACD was added gene: ACD was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Literature Mode of inheritance for gene: ACD was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ACD were set to 31515401; 27807141; 25205116 Phenotypes for gene: ACD were set to pulmonary fibrosis and/or bone marrow failure, telomere-related MONDO:0000148 Mode of pathogenicity for gene: ACD was set to Other Review for gene: ACD was set to AMBER Added comment: 3 probands reported with heterozygous variants (only 2 of the variants including p.Lys170 look to possibly relevant) PMID: 31515401 - proband 1 with bone marrow failure and pulmonary fibrosis in the context of a telomere syndrome heterozygous for recurrent p.Lys170del. Proband 2 with idiopathic pulmonary fibrosis heterozygous for p.Lys170Glu. Proband 3 with idiopathic pulmonary fibrosis heterozygous for p.Ala72Glu (9 hets in gnomAD - VUS), which was also found in the unaffected 83 yo father. All patients had a leukocyte telomere length <1st percentiles for age. PMID: 27807141 - in vitro functional assays suggesting that the recurrent variant p.Lys170del is sufficient to cause the cellular underpinnings of dyskeratosis congenita, acting in a dosage-dependent mechanism rather than dominant-negative. PMID: 25205116 - Lys170del identified in 18-yo proband, mother, and maternal grandmother presented with bone marrow failure of varying severity, and decreasing ages of presentation in successive generations. All with short telomeres. In vitro assays demonstrate the variant localises to telomeres but fails to recruit telomerase to telomeres. Sources: Literature |
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| Pulmonary Fibrosis_Interstitial Lung Disease v0.17 | FOXF1 |
Zornitza Stark gene: FOXF1 was added gene: FOXF1 was added to Pulmonary Fibrosis_Interstitial Lung Disease. Sources: Expert Review Mode of inheritance for gene: FOXF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FOXF1 were set to 23505205; 27071622; 27855150; 19500772 Phenotypes for gene: FOXF1 were set to Alveolar capillary dysplasia with misalignment of pulmonary veins, MIM# 265380 Review for gene: FOXF1 was set to GREEN Added comment: Congenital alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is characterized histologically by failure of formation and ingrowth of alveolar capillaries that then do not make contact with alveolar epithelium, medial muscular thickening of small pulmonary arterioles with muscularization of the intraacinar arterioles, thickened alveolar walls, and anomalously situated pulmonary veins running alongside pulmonary arterioles and sharing the same adventitial sheath. Less common features include a reduced number of alveoli and a patchy distribution of the histopathologic changes. The disorder is associated with persistent pulmonary hypertension of the neonate and shows varying degrees of lability and severity. Affected infants present with respiratory distress resulting from pulmonary hypertension in the early postnatal period, and the disease is uniformly fatal within the newborn period. Additional features of ACDMPV include multiple congenital anomalies affecting the cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems, as well as disruption of the normal right-left asymmetry of intrathoracic or intraabdominal organs. Over 50 families reported. Most are sporadic, but a few inherited, generally from mother, incomplete paternal imprinting of this gene has been suggested. Mechanism is LOF, many variants located in the DNA binding domain. Sources: Expert Review |
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