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| Likely inborn error of metabolism v9.13 | ASPA | Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v9.13 | ASPA | Ida Ertmanska Phenotypes for gene: ASPA were changed from Canavan disease to Canavan disease, OMIM:271900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Likely inborn error of metabolism v9.10 | FOCAD |
Ida Ertmanska changed review comment from: PMID: 35864190 Traspas et al., 2022 Report of 14 children from ten unrelated families (various ancestries, 6/10 families were consanguineous) presenting with a syndromic form of pediatric liver cirrhosis. WGS/WES detected biallelic FOCAD variants which segregate with disease. FOCAD variants detected: 3 missense, 3 stop-gain, 2 frameshift, 5 splicing, and 1 large deletion. LOF is the mechanism of disease. Absence of FOCAD protein shown in F1 and F2 individuals. The liver phenotype was marked by cirrhosis (71.4%) with multinodularity (57.1%). Intrahepatic cholestasis was diagnosed in 35.7% of the patients, with associated jaundice (35.7%) and biliary hyperplasia (28.6%). Splenomegaly and hepatomegaly also deteced in 71% of patients. In one case, liver transplant was necessary at 6 months of age. Additional non-liver related phenotypes: abdominal distension (78.6%), diarrhea (57.1%), as well as metabolic anomalies (85.7%), hernias, IUGR. Congenital cardiac and genitourinary anomalies present in 42% of patients. 6 children passed away due to hepatic or multiorgan failure (5 before age 1 year). Moreover, focad-/- knockout zebrafish phenocopied the human disease, revealing altered mRNA degradation processes in the liver. Further reports (articles not curated in detail): PMID: 40662096 - Tarrell et al., 2025 - Hispanic male infant with neonatal liver disease - comp het for FOCAD c.1532A > G; p.Tyr511Cys and c.5137C > A; p.Pro1713Thr - both variants VUS, may explain milder disease progression (no liver failure or cirrhosis) PMID: 41189834 Raja et al., 2025 - neonatal case with liver cirrhosis, required liver transplant at 3 months of age - comp het for FOCAD c.4435del p.Lys1475Asnfs* and exon 6-7 deletion PMID: 41608453 Nuzhnaya et al., 2026 - 3yo male patient with infantile liver cirrhosis and neutropenia, homozygous for a novel FOCAD splice-site variant NM_001375570.1:c.1455 + 1G > T, p.Thr475_Val486del; liver transplant performed at 25 months This gene is associated with AR Liver disease, severe congenital, OMIM:619991 in OMIM (Accessed 11th May 2026). Not yet curated in ClinGen or G2P. Sources: Literature; to: PMID: 35864190 Traspas et al., 2022 Report of 14 children from ten unrelated families (various ancestries, 6/10 families were consanguineous) presenting with a syndromic form of pediatric liver cirrhosis. WGS/WES detected biallelic FOCAD variants which segregate with disease. FOCAD variants detected: 3 missense, 3 stop-gain, 2 frameshift, 5 splicing, and 1 large deletion. LOF is the mechanism of disease. Absence of FOCAD protein shown in F1 and F2 individuals. The liver phenotype was marked by cirrhosis (71.4%) with multinodularity (57.1%). Intrahepatic cholestasis was diagnosed in 35.7% of the patients, with associated jaundice (35.7%) and biliary hyperplasia (28.6%). Splenomegaly and hepatomegaly also deteced in 71% of patients. In one case, liver transplant was necessary at 6 months of age. Additional non-liver related phenotypes: abdominal distension (78.6%), diarrhea (57.1%), as well as metabolic anomalies (85.7% - e.g., steatosis, increased glycogen content, iron overload), hernias, IUGR. Congenital cardiac and genitourinary anomalies present in 42% of patients. 6 children passed away due to hepatic or multiorgan failure (5 before age 1 year). Moreover, focad-/- knockout zebrafish phenocopied the human disease, revealing altered mRNA degradation processes in the liver. Further reports (articles not curated in detail): PMID: 40662096 - Tarrell et al., 2025 - Hispanic male infant with neonatal liver disease - comp het for FOCAD c.1532A > G; p.Tyr511Cys and c.5137C > A; p.Pro1713Thr - both variants VUS, may explain milder disease progression (no liver failure or cirrhosis) PMID: 41189834 Raja et al., 2025 - neonatal case with liver cirrhosis, required liver transplant at 3 months of age - comp het for FOCAD c.4435del p.Lys1475Asnfs* and exon 6-7 deletion PMID: 41608453 Nuzhnaya et al., 2026 - 3yo male patient with infantile liver cirrhosis and neutropenia, homozygous for a novel FOCAD splice-site variant NM_001375570.1:c.1455 + 1G > T, p.Thr475_Val486del; liver transplant performed at 25 months This gene is associated with AR Liver disease, severe congenital, OMIM:619991 in OMIM (Accessed 11th May 2026). Not yet curated in ClinGen or G2P. Sources: Literature |
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| Likely inborn error of metabolism v9.10 | FOCAD |
Ida Ertmanska gene: FOCAD was added gene: FOCAD was added to Likely inborn error of metabolism. Sources: Literature Q2_26_promote_green, Q2_26_expert_review tags were added to gene: FOCAD. Mode of inheritance for gene: FOCAD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FOCAD were set to 35864190; 40662096; 41189834; 41608453 Phenotypes for gene: FOCAD were set to Liver disease, severe congenital, OMIM:619991; liver disease, severe congenital, MONDO:0859273 Review for gene: FOCAD was set to GREEN Added comment: PMID: 35864190 Traspas et al., 2022 Report of 14 children from ten unrelated families (various ancestries, 6/10 families were consanguineous) presenting with a syndromic form of pediatric liver cirrhosis. WGS/WES detected biallelic FOCAD variants which segregate with disease. FOCAD variants detected: 3 missense, 3 stop-gain, 2 frameshift, 5 splicing, and 1 large deletion. LOF is the mechanism of disease. Absence of FOCAD protein shown in F1 and F2 individuals. The liver phenotype was marked by cirrhosis (71.4%) with multinodularity (57.1%). Intrahepatic cholestasis was diagnosed in 35.7% of the patients, with associated jaundice (35.7%) and biliary hyperplasia (28.6%). Splenomegaly and hepatomegaly also deteced in 71% of patients. In one case, liver transplant was necessary at 6 months of age. Additional non-liver related phenotypes: abdominal distension (78.6%), diarrhea (57.1%), as well as metabolic anomalies (85.7%), hernias, IUGR. Congenital cardiac and genitourinary anomalies present in 42% of patients. 6 children passed away due to hepatic or multiorgan failure (5 before age 1 year). Moreover, focad-/- knockout zebrafish phenocopied the human disease, revealing altered mRNA degradation processes in the liver. Further reports (articles not curated in detail): PMID: 40662096 - Tarrell et al., 2025 - Hispanic male infant with neonatal liver disease - comp het for FOCAD c.1532A > G; p.Tyr511Cys and c.5137C > A; p.Pro1713Thr - both variants VUS, may explain milder disease progression (no liver failure or cirrhosis) PMID: 41189834 Raja et al., 2025 - neonatal case with liver cirrhosis, required liver transplant at 3 months of age - comp het for FOCAD c.4435del p.Lys1475Asnfs* and exon 6-7 deletion PMID: 41608453 Nuzhnaya et al., 2026 - 3yo male patient with infantile liver cirrhosis and neutropenia, homozygous for a novel FOCAD splice-site variant NM_001375570.1:c.1455 + 1G > T, p.Thr475_Val486del; liver transplant performed at 25 months This gene is associated with AR Liver disease, severe congenital, OMIM:619991 in OMIM (Accessed 11th May 2026). Not yet curated in ClinGen or G2P. Sources: Literature |
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| Likely inborn error of metabolism v1.47 | ASPA |
Ivone Leong Source NHS GMS was added to ASPA. Source London North GLH was added to ASPA. |
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| Likely inborn error of metabolism v0.4 | NAT8L |
Ellen McDonagh gene: NAT8L was added gene: NAT8L was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: NAT8L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NAT8L were set to 19807691 Phenotypes for gene: NAT8L were set to ?N-acetylaspartate deficiency 614063 |
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| Likely inborn error of metabolism v0.4 | ASPA |
Ellen McDonagh gene: ASPA was added gene: ASPA was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: ASPA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASPA were set to 27604308 Phenotypes for gene: ASPA were set to Canavan disease |
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| Likely inborn error of metabolism v0.4 | AGA |
Ellen McDonagh gene: AGA was added gene: AGA was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: AGA was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AGA were set to 27604308 Phenotypes for gene: AGA were set to Aspartylglucosaminuria |
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