Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
11 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.13 | LAMP3 | Ida Ertmanska changed review comment from: Comment on list classification: There are now 13 individuals from 5 unrelated families reported in literature with biallelic LAMP3 variants. 4/13 individuals were clinically asymptomatic. However, one of these individuals had signs of lung fibrosis on CT scans. In addition, two individuals were possibly pre-symptomatic - aged 14 months and 4 years at time of report. There is good functional evidence from lung epithelial cells, as well as dog and mouse models, to support this association. Hence, this gene should be promoted to Green at the next update.; to: Comment on list classification: There are now 13 individuals from 5 unrelated families reported in literature with biallelic LAMP3 variants. There are at least 3 unrelated probands that presented with severe neonatal respiratory failure and ground glass opacities seen on lung CT scans. 4/13 individuals were clinically asymptomatic. However, one of these individuals had signs of lung fibrosis on CT scans. In addition, two individuals were possibly pre-symptomatic - aged 14 months and 4 years at time of report. There is good functional evidence from lung epithelial cells, as well as dog and mouse models, to support this association. Hence, this gene should be promoted to Green at the next update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.13 | LAMP3 | Ida Ertmanska Classified gene: LAMP3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.13 | LAMP3 | Ida Ertmanska Added comment: Comment on list classification: There are now 13 individuals from 5 unrelated families reported in literature with biallelic LAMP3 variants. 4/13 individuals were clinically asymptomatic. However, one of these individuals had signs of lung fibrosis on CT scans. In addition, two individuals were possibly pre-symptomatic - aged 14 months and 4 years at time of report. There is good functional evidence from lung epithelial cells, as well as dog and mouse models, to support this association. Hence, this gene should be promoted to Green at the next update. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.13 | LAMP3 | Ida Ertmanska Gene: lamp3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.12 | LAMP3 | Ida Ertmanska Publications for gene: LAMP3 were set to 40023045 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.11 | LAMP3 | Ida Ertmanska edited their review of gene: LAMP3: Changed publications to: 32150563, 34161347, 40023045, 41653023 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.11 | LAMP3 |
Ida Ertmanska changed review comment from: PMID: 40023045 Louvrier et al., 2025 Two heterozygous LAMP3 variants (Y302Qfs∗2 and T268M) were identified in a male proband with childhood interstitial lung disease. The individual is a 15-year-old boy born to North African distant consanguineous parents, had no neonatal respiratory distress but presented with a cough and dyspnoea on exertion at the age of 9 years. Chest CT scan showed severe ILD lesions with ground glass opacities and signs of lung fibrosis. Seq method: trio exome sequencing. PMID: 41653023 Keehan et al., 2026 13 participants from 5 unrelated families were identified with biallelic variants in LAMP3 (1 has been reported previously). They presented with variable phenotypes ranging from neonatal respiratory distress to asymptomatic in adulthood. Probands underwent either exome or genome sequencing, with segregation confirmed by Sanger seq. F1: female proband homozygous for NM_014398.4 LAMP3: c.247del p.(Ile83PhefsTer47); she presented with severe neonatal respiratory failure; serial lung CT studies demonstrate a progression from ground glass opacities (GGO) in early life to fibrotic changes in adolescence. F2: 3 sibs comp het for LAMP3 variants NM_014398:c.38C>A p.(Ala13Glu) and NM_014398:c.1162G>A p.(Gly388Arg). Two older sisters presented with severe neonatal respiratory failure; lung CT imaging that demonstrated GGO and cystic lung disease. In contrast, their younger brother has no history of respiratory symptoms and had unremarkable lung CT imaging at age 14 months. F3: 7 individuals from an extended consanguineous family, homozygous for LAMP3 NM_014398.4:c.862G>A p.(Gly288Arg). 3/7 individuals are clinically asymptomatic, though a chest CT scan revealed areas of GGO and uneven aeration at age 38 yrs. 2 other family members homozygous for the variant were asymptomatic at age 4 and 47 yrs. F4: Male proband, homozygous for an intronic variant in LAMP3 NM_014398.4:c.49+1G>A p.?. He presented with severe neonatal respiratory failure, and lung imaging studies demonstrated diffuse GGO with uneven aeration at age 2 years. F5: Patient described previously in PMID: 40023045 Louvrier et al., 2025. The association between LAMP3 and AR inherited interstitial lung disease has been classified as Definitive in ClinGen (Interstitial Lung Disease Expert Panel, 08/18/2026). Sources: Literature; to: PMID: 40023045 Louvrier et al., 2025 Two heterozygous LAMP3 variants (Y302Qfs∗2 and T268M) were identified in a male proband with childhood interstitial lung disease. The individual is a 15-year-old boy born to North African distant consanguineous parents, had no neonatal respiratory distress but presented with a cough and dyspnoea on exertion at the age of 9 years. Chest CT scan showed severe ILD lesions with ground glass opacities and signs of lung fibrosis. Seq method: trio exome sequencing. PMID: 41653023 Keehan et al., 2026 13 participants from 5 unrelated families were identified with biallelic variants in LAMP3 (1 has been reported previously). They presented with variable phenotypes ranging from neonatal respiratory distress to asymptomatic in adulthood. Probands underwent either exome or genome sequencing, with segregation confirmed by Sanger seq. F1: female proband homozygous for NM_014398.4 LAMP3: c.247del p.(Ile83PhefsTer47); she presented with severe neonatal respiratory failure; serial lung CT studies demonstrate a progression from ground glass opacities (GGO) in early life to fibrotic changes in adolescence. F2: 3 sibs comp het for LAMP3 variants NM_014398:c.38C>A p.(Ala13Glu) and NM_014398:c.1162G>A p.(Gly388Arg). Two older sisters presented with severe neonatal respiratory failure; lung CT imaging that demonstrated GGO and cystic lung disease. In contrast, their younger brother has no history of respiratory symptoms and had unremarkable lung CT imaging at age 14 months. F3: 7 individuals from an extended consanguineous family, homozygous for LAMP3 NM_014398.4:c.862G>A p.(Gly288Arg). 3/7 individuals are clinically asymptomatic, though a chest CT scan revealed areas of GGO and uneven aeration at age 38 yrs. 2 other family members homozygous for the variant were asymptomatic at age 4 and 47 yrs. F4: Male proband, homozygous for an intronic variant in LAMP3 NM_014398.4:c.49+1G>A p.?. He presented with severe neonatal respiratory failure, and lung imaging studies demonstrated diffuse GGO with uneven aeration at age 2 years. F5: Patient described previously in PMID: 40023045 Louvrier et al., 2025. Functional studies in lung epithelial cells demonstrate that some of the LAMP3 variants identified in this cohort cause decreased cell proliferation, induced ER stress, activation of apoptotic pathways, or abnormal protein glycosylation. Variants p.(Gly288Arg) and p.(Gly388Arg) were found to cause abnormalities in the growth of lung A549 epithelial cells. Other functional studies as listed in ClinGen curation: Human Protein Atlas shows protein expression in Lung, Lymph node, and Tonsil tissues only. PMID: 32150563 Dillard et al., 2020 - homozygous for the c.1159G>A (p.Glu387Lys) variant was found to be associated with defect in lamellar body biogenesis and fatal neonatal interstitial lung disease in dogs. PMID: 34161347 Lunding et al., 2021 - Lamp3 knockout mice display regular lung function under basal conditions, aggravated by ovalbumin-induced experimental allergic asthma. The levels of a major hydrophobic protein component of pulmonary surfactant, SP-C, are strongly increased in the lung of Lamp3 knockout mice, and the lipid composition of the bronchoalveolar lavage shows mild but significant changes, resulting in alterations in surfactant functionality. The association between LAMP3 and AR inherited interstitial lung disease has been classified as Definitive in ClinGen (Interstitial Lung Disease Expert Panel, 08/18/2026). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.11 | LAMP3 |
Ida Ertmanska changed review comment from: PMID: 40023045 Louvrier et al., 2025 Two heterozygous LAMP3 variants (Y302Qfs∗2 and T268M) were identified in a male proband with childhood interstitial lung disease. The individual is a 15-year-old boy born to North African distant consanguineous parents, had no neonatal respiratory distress but presented with a cough and dyspnoea on exertion at the age of 9 years. Chest CT scan showed severe ILD lesions with ground glass opacities and signs of lung fibrosis. Seq method: trio exome sequencing. PMID: 41653023 Keehan et al,, 2026 13 participants from 5 unrelated families were identified with biallelic variants in LAMP3 (1 has been reported previously). They presented with variable phenotypes ranging from neonatal respiratory distress to asymptomatic in adulthood. Probands underwent either exome or genome sequencing, with segregation confirmed by Sanger seq. F1: female proband homozygous for NM_014398.4 LAMP3: c.247del p.(Ile83PhefsTer47); she presented with severe neonatal respiratory failure; serial lung CT studies demonstrate a progression from ground glass opacities (GGO) in early life to fibrotic changes in adolescence. F2: 3 sibs comp het for LAMP3 variants NM_014398:c.38C>A p.(Ala13Glu) and NM_014398:c.1162G>A p.(Gly388Arg). Two older sisters presented with severe neonatal respiratory failure; lung CT imaging that demonstrated GGO and cystic lung disease. In contrast, their younger brother has no history of respiratory symptoms and had unremarkable lung CT imaging at age 14 months. F3: 7 individuals from an extended consanguineous family, homozygous for LAMP3 NM_014398.4:c.862G>A p.(Gly288Arg). 3/7 individuals are clinically asymptomatic, though a chest CT scan revealed areas of GGO and uneven aeration at age 38 yrs. 2 other family members homozygous for the variant were asymptomatic at age 4 and 47 yrs. F4: Male proband, homozygous for an intronic variant in LAMP3 NM_014398.4:c.49+1G>A p.?. He presented with severe neonatal respiratory failure, and lung imaging studies demonstrated diffuse GGO with uneven aeration at age 2 years. F5: Patient described previously in PMID: 40023045 Louvrier et al., 2025. The association between LAMP3 and AR inherited interstitial lung disease has been classified as Definitive in ClinGen (Interstitial Lung Disease Expert Panel, 08/18/2026). Sources: Literature; to: PMID: 40023045 Louvrier et al., 2025 Two heterozygous LAMP3 variants (Y302Qfs∗2 and T268M) were identified in a male proband with childhood interstitial lung disease. The individual is a 15-year-old boy born to North African distant consanguineous parents, had no neonatal respiratory distress but presented with a cough and dyspnoea on exertion at the age of 9 years. Chest CT scan showed severe ILD lesions with ground glass opacities and signs of lung fibrosis. Seq method: trio exome sequencing. PMID: 41653023 Keehan et al., 2026 13 participants from 5 unrelated families were identified with biallelic variants in LAMP3 (1 has been reported previously). They presented with variable phenotypes ranging from neonatal respiratory distress to asymptomatic in adulthood. Probands underwent either exome or genome sequencing, with segregation confirmed by Sanger seq. F1: female proband homozygous for NM_014398.4 LAMP3: c.247del p.(Ile83PhefsTer47); she presented with severe neonatal respiratory failure; serial lung CT studies demonstrate a progression from ground glass opacities (GGO) in early life to fibrotic changes in adolescence. F2: 3 sibs comp het for LAMP3 variants NM_014398:c.38C>A p.(Ala13Glu) and NM_014398:c.1162G>A p.(Gly388Arg). Two older sisters presented with severe neonatal respiratory failure; lung CT imaging that demonstrated GGO and cystic lung disease. In contrast, their younger brother has no history of respiratory symptoms and had unremarkable lung CT imaging at age 14 months. F3: 7 individuals from an extended consanguineous family, homozygous for LAMP3 NM_014398.4:c.862G>A p.(Gly288Arg). 3/7 individuals are clinically asymptomatic, though a chest CT scan revealed areas of GGO and uneven aeration at age 38 yrs. 2 other family members homozygous for the variant were asymptomatic at age 4 and 47 yrs. F4: Male proband, homozygous for an intronic variant in LAMP3 NM_014398.4:c.49+1G>A p.?. He presented with severe neonatal respiratory failure, and lung imaging studies demonstrated diffuse GGO with uneven aeration at age 2 years. F5: Patient described previously in PMID: 40023045 Louvrier et al., 2025. The association between LAMP3 and AR inherited interstitial lung disease has been classified as Definitive in ClinGen (Interstitial Lung Disease Expert Panel, 08/18/2026). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.11 | LAMP3 | Ida Ertmanska edited their review of gene: LAMP3: Changed publications to: 40023045, 41653023 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.11 | LAMP3 |
Ida Ertmanska changed review comment from: PMID: 40023045 Louvrier et al., 2025 Two heterozygous LAMP3 variants (Y302Qfs∗2 and T268M) were identified in a 15 year old boy with childhood interstitial lung disease. PMID: 41653023 Keehan et al,, 2026 13 participants were identified with biallelic variants in LAMP3. They presented with variable phenotypes ranging from neonatal respiratory distress to asymptomatic in adulthood The association between LAMP3 and AR inherited interstitial lung disease has been classified as Definitive in ClinGen (Interstitial Lung Disease Expert Panel, 08/18/2026). Sources: Literature; to: PMID: 40023045 Louvrier et al., 2025 Two heterozygous LAMP3 variants (Y302Qfs∗2 and T268M) were identified in a male proband with childhood interstitial lung disease. The individual is a 15-year-old boy born to North African distant consanguineous parents, had no neonatal respiratory distress but presented with a cough and dyspnoea on exertion at the age of 9 years. Chest CT scan showed severe ILD lesions with ground glass opacities and signs of lung fibrosis. Seq method: trio exome sequencing. PMID: 41653023 Keehan et al,, 2026 13 participants from 5 unrelated families were identified with biallelic variants in LAMP3 (1 has been reported previously). They presented with variable phenotypes ranging from neonatal respiratory distress to asymptomatic in adulthood. Probands underwent either exome or genome sequencing, with segregation confirmed by Sanger seq. F1: female proband homozygous for NM_014398.4 LAMP3: c.247del p.(Ile83PhefsTer47); she presented with severe neonatal respiratory failure; serial lung CT studies demonstrate a progression from ground glass opacities (GGO) in early life to fibrotic changes in adolescence. F2: 3 sibs comp het for LAMP3 variants NM_014398:c.38C>A p.(Ala13Glu) and NM_014398:c.1162G>A p.(Gly388Arg). Two older sisters presented with severe neonatal respiratory failure; lung CT imaging that demonstrated GGO and cystic lung disease. In contrast, their younger brother has no history of respiratory symptoms and had unremarkable lung CT imaging at age 14 months. F3: 7 individuals from an extended consanguineous family, homozygous for LAMP3 NM_014398.4:c.862G>A p.(Gly288Arg). 3/7 individuals are clinically asymptomatic, though a chest CT scan revealed areas of GGO and uneven aeration at age 38 yrs. 2 other family members homozygous for the variant were asymptomatic at age 4 and 47 yrs. F4: Male proband, homozygous for an intronic variant in LAMP3 NM_014398.4:c.49+1G>A p.?. He presented with severe neonatal respiratory failure, and lung imaging studies demonstrated diffuse GGO with uneven aeration at age 2 years. F5: Patient described previously in PMID: 40023045 Louvrier et al., 2025. The association between LAMP3 and AR inherited interstitial lung disease has been classified as Definitive in ClinGen (Interstitial Lung Disease Expert Panel, 08/18/2026). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood interstitial lung disease v1.11 | LAMP3 |
Ida Ertmanska gene: LAMP3 was added gene: LAMP3 was added to Childhood interstitial lung disease. Sources: Literature Q3_26_promote_green tags were added to gene: LAMP3. Mode of inheritance for gene: LAMP3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LAMP3 were set to 40023045 Phenotypes for gene: LAMP3 were set to interstitial lung disease specific to childhood, MONDO:0017014 Review for gene: LAMP3 was set to GREEN Added comment: PMID: 40023045 Louvrier et al., 2025 Two heterozygous LAMP3 variants (Y302Qfs∗2 and T268M) were identified in a 15 year old boy with childhood interstitial lung disease. PMID: 41653023 Keehan et al,, 2026 13 participants were identified with biallelic variants in LAMP3. They presented with variable phenotypes ranging from neonatal respiratory distress to asymptomatic in adulthood The association between LAMP3 and AR inherited interstitial lung disease has been classified as Definitive in ClinGen (Interstitial Lung Disease Expert Panel, 08/18/2026). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||