Full Report

Format

Full Report
Summary (Text)
Summary (XML)

Send to:

Choose Destination

File
Clipboard
Collections

Links from Gene

Autosomal dominant aplasia and myelodysplasia(BMFS1)

MedGen UID:: 814883
•Concept ID:: C3808553
•: Disease or Syndrome

Synonym:	Bone marrow failure syndrome 1
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	SRP72 (4q12)

Monarch Initiative:	MONDO:0013851
OMIM®:	614675
Orphanet:	ORPHA314399

Definition

Bone marrow failure syndrome-1 (BMFS1) is an autosomal dominant condition characterized by early-onset aplastic anemia or pancytopenia in some patients, and adult-onset myelodysplasia in others. Deafness or labyrinthitis also has been observed in affected individuals (Kirwan et al., 2012). Genetic Heterogeneity of Bone Marrow Failure Syndrome See also BMFS2 (615715), caused by mutation in the ERCC6L2 gene (615667) on chromosome 9q22; BMFS3 (617052), caused by mutation in the DNAJC21 gene (617048) on chromosome 5p13; BMFS4 (618116), caused by mutation in the MYSM1 gene (612176) on chromosome 1p32; BMFS5 (618165), caused by mutation in the TP53 gene (191170) on chromosome 17p13; BMFS6 (618849), caused by mutation in the MDM4 gene (602704) on chromosome 1q32; BMFS7 (AMEDS; 619151), caused by mutation in the ADH5 gene (103710) on chromosome 4q accompanied by a specific mutation in the ALDH2 gene (100650) on chromosome 12q24; and BMFS8 (ZHS; 620501), caused by mutation in the SLC30A7 gene (611149) on chromosome 1p21. [from OMIM]

Clinical features

From HPO

Myelodysplasia

MedGen UID:: 10231
•Concept ID:: C0026985
•: Congenital Abnormality

Clonal hematopoietic stem cell disorders characterized by dysplasia (ineffective production) in one or more hematopoietic cell lineages, leading to anemia and cytopenia.

See: Feature record | Search on this feature

Sensorineural hearing loss disorder

MedGen UID:: 9164
•Concept ID:: C0018784
•: Disease or Syndrome

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

See: Feature record | Search on this feature

Aplastic anemia

MedGen UID:: 8063
•Concept ID:: C0002874
•: Disease or Syndrome

Aplastic anemia is a serious disorder of the bone marrow that affects between 2 and 5 persons per million per year. About 75% of these cases are classified as idiopathic (Young, 2000). In about 15% of cases a drug or infection can be identified that precipitates the aplasia, although why only some individuals are susceptible is unclear. In about 5 to 10% of patients, the aplastic anemia is constitutional--i.e., is familial or presents with one or more associated somatic abnormalities (summary by Vulliamy et al., 2002).

See: Feature record | Search on this feature

Pancytopenia

MedGen UID:: 18281
•Concept ID:: C0030312
•: Disease or Syndrome

An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).

See: Feature record | Search on this feature

Bone marrow hypocellularity

MedGen UID:: 383749
•Concept ID:: C1855710
•: Finding

A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.

See: Feature record | Search on this feature

Show all Hide all

Abnormality of blood and blood-forming tissues
Ear malformation
- Sensorineural hearing loss disorder
Neoplasm
- Myelodysplasia

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVAutosomal dominant aplasia and myelodysplasia

Inherited aplastic anemia
- Autosomal dominant aplasia and myelodysplasia

Recent clinical studies

Etiology

Germ line variants in patients with acute myeloid leukemia without a suspicion of hereditary hematologic malignancy syndrome.

Guijarro F, López-Guerra M, Morata J, Bataller A, Paz S, Cornet-Masana JM, Banús-Mulet A, Cuesta-Casanovas L, Carbó JM, Castaño-Díez S, Jiménez-Vicente C, Cortés-Bullich A, Triguero A, Martínez-Roca A, Esteban D, Gómez-Hernando M, Álamo Moreno JR, López-Oreja I, Garrote M, Risueño RM, Tonda R, Gut I, Colomer D, Díaz-Beya M, Esteve J
Blood Adv 2023 Oct 10;7(19):5799-5811. doi: 10.1182/bloodadvances.2023009742. PMID: 37450374 Free PMC Article

Myelodysplasia in autosomal dominant and sporadic monocytopenia immunodeficiency syndrome: diagnostic features and clinical implications.

Calvo KR, Vinh DC, Maric I, Wang W, Noel P, Stetler-Stevenson M, Arthur DC, Raffeld M, Dutra A, Pak E, Myung K, Hsu AP, Hickstein DD, Pittaluga S, Holland SM
Haematologica 2011 Aug;96(8):1221-5. Epub 2011 Apr 20 doi: 10.3324/haematol.2011.041152. PMID: 21508125 Free PMC Article

A family inheriting different subtypes of acute myelogenous leukemia.

Horwitz M, Sabath DE, Smithson WA, Radich J
Am J Hematol 1996 Aug;52(4):295-304. doi: 10.1002/(SICI)1096-8652(199608)52:4<295::AID-AJH9>3.0.CO;2-N. PMID: 8701948

Kostmann's disease, recombinant HuG-CSF, monosomy 7 and MDS/AML.

Smith OP, Reeves BR, Kempski HM, Evans JP
Br J Haematol 1995 Sep;91(1):150-3. doi: 10.1111/j.1365-2141.1995.tb05260.x. PMID: 7577623

See all (4)

Diagnosis

Germ line variants in patients with acute myeloid leukemia without a suspicion of hereditary hematologic malignancy syndrome.

Myelodysplasia in autosomal dominant and sporadic monocytopenia immunodeficiency syndrome: diagnostic features and clinical implications.

Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy.

Owen CJ, Toze CL, Koochin A, Forrest DL, Smith CA, Stevens JM, Jackson SC, Poon MC, Sinclair GD, Leber B, Johnson PR, Macheta A, Yin JA, Barnett MJ, Lister TA, Fitzgibbon J
Blood 2008 Dec 1;112(12):4639-45. Epub 2008 Aug 21 doi: 10.1182/blood-2008-05-156745. PMID: 18723428

A family inheriting different subtypes of acute myelogenous leukemia.

Horwitz M, Sabath DE, Smithson WA, Radich J
Am J Hematol 1996 Aug;52(4):295-304. doi: 10.1002/(SICI)1096-8652(199608)52:4<295::AID-AJH9>3.0.CO;2-N. PMID: 8701948

See all (4)