Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: ACD
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Immunodeficiency may be part of the syndromic picture of dyskeratosis congenita, especially where associated with bone marrow failureCreated: 18 Jun 2018, 3:49 p.m.
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
Dyskeratosis congenita; Hoyeraal-Hreidarsson syndrome
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Comment on phenotypes: Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, recurrent infections. Severe phenotype with developmental delay and cerebellar hypoplasia;Combined immunodeficiencies with associated or syndromic featuresCreated: 5 Jul 2018, 2:39 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TPP1 .PanelApp HGNC gene symbol check: ACD . IUIS Disease: AD/AR -DKC due to TPP1 deficiency . IUIS Inheritance: AD or AR .T cells: N/A, .B cells: Variable, .IUIS Other affected cells: N/A. IUIS Associated features: Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair and eyelashes, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, +/- recurrent infections. A severe phenotype with developmental delay and cerebellar hypoplasia known as Hoyeraal-Hreidarsson Syndrome (HHS) may occur in some DKC patients. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: DyskeratosIs Congenita (DKC), Myelodysplasia, Short TelomeresCreated: 5 Jul 2018, 2:32 p.m.
Comment on list classification: Changed Amber to Green from external clinical review commentCreated: 20 Jun 2018, 2:31 p.m.
Only two cases reported since 2015 but in view of external clinical review this gene was made greenCreated: 20 Jun 2018, 2:29 p.m.
Comment on mode of inheritance: changed MOI from external review suggestionCreated: 20 Jun 2018, 2:27 p.m.
Comment on phenotypes: added phenotype suggested by expert reviewerCreated: 20 Jun 2018, 2:27 p.m.
Genetic variants of the gene ACD results in a Antibody Deficiencies type pf PID, where severely reduced serum immunoglobulins (Igs) with profoundly decreased or absent B cells (agammaglobulinemia) is observed. This type of PID is caused by: myelodysplasia with hypogammaglobuline mia (monosomy 7, trisomy 8, or dyskeratosis congenita), and thymoma with immunodeficiency with unknown genetic defect.Created: 30 Apr 2018, 1:33 p.m.
Kept as amber until further evidence, no additional families in the literature since 2015. Added watch-list tag.Created: 30 Apr 2018, 1:18 p.m.
Comment on publications: Added publications to support Dyskeratosis Congenita, which is a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. There is currently (since 2015) only two families been described, one one family with autosomal dominant inheritance had only progressive bone marrow failure and one patient (patient B) with autosomal recessive inheritance had a more severe phenotype.Created: 30 Apr 2018, 1:18 p.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.Created: 20 Apr 2018, 12:25 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: ACD, GRID_Gene_Symbol: ACD, GRID_Transcript_ENS_Community submitted: ENST00000219251, GRID_Transcript_RefSeq: NM_001082486.1, GRID_Transcript_ENS_used_on_Production: ENST00000219251Created: 17 Apr 2018, 12:12 p.m.
Phenotypes for gene: ACD were changed from Dyskeratosis congenita 6, 616553; Dyskeratosis congenita 7, 616553; Hoyeraal-Hreidarsson syndrome to Dyskeratosis congenita, autosomal dominant 6, OMIM:616553; Dyskeratosis congenita, autosomal recessive 7, OMIM:616553
Source NHS GMS was added to ACD.
Source North West GLH was added to ACD.
Source London North GLH was added to ACD.
Tag watchlist was removed from gene: ACD.
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Phenotypes for gene: ACD were set to Dyskeratosis congenita 6, 616553; Dyskeratosis congenita 7, 616553; Hoyeraal-Hreidarsson syndrome
Phenotypes for gene: ACD were set to Dyskeratosis congenita 6, 616553; Dyskeratosis congenita 7, 616553; Hoyeraal-Hreidarsson syndrome; Intrauterine growth retardation, microcephaly, nail dystrophy, sparse scalp hair, hyperpigmentation of skin, palmar hyperkeratosis, premalignant oral leukoplakia, pancytopenia, myelodysplasia, recurrent infections; Severe phenotype with developmental delay and cerebellar hypoplasia; Combined immunodeficiencies with associated or syndromic features
Gene: acd has been classified as Green List (High Evidence).
Gene: acd has been classified as Green List (High Evidence).
Mode of inheritance for gene: ACD was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: ACD were set to Dyskeratosis congenita 6, 616553; Dyskeratosis congenita 7, 616553; Hoyeraal-Hreidarsson syndrome
Phenotypes for ACD were set to Dyskeratosis congenita 6, 616553; Dyskeratosis congenita 7, 616553
Publications for ACD were set to 25205116; 25233904
Publications for ACD were set to 25205116; 25233904
Phenotypes for ACD were set to Dyskeratosis congenita 6; Dyskeratosis congenita 7
Expert Review Amber was added to ACD. Panel: Primary immunodeficiency disorders
Phenotypes for gene ACD were set to Dyskeratosis congenita 6, Dyskeratosis congenita 7, Dyskeratosis congenita 7
ACD was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
ACD was created by Louise Daugherty