BMFS3
MCID: BNM013
MIFTS: 27

Bone Marrow Failure Syndrome 3 (BMFS3)

Categories: Blood diseases, Bone diseases, Genetic diseases, Immune diseases, Rare diseases, Skin diseases

Aliases & Classifications for Bone Marrow Failure Syndrome 3

MalaCards integrated aliases for Bone Marrow Failure Syndrome 3:

Name: Bone Marrow Failure Syndrome 3 57 72 29 6
Bmfs3 57 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
onset in in infancy or early childhood
possible cancer predisposition
bone marrow hypocellularity may improve spontaneously with age


HPO:

31
bone marrow failure syndrome 3:
Inheritance autosomal recessive inheritance
Onset and clinical course phenotypic variability


Classifications:



Summaries for Bone Marrow Failure Syndrome 3

OMIM® : 57 Bone marrow failure syndrome-3 is an autosomal recessive disorder characterized by onset of pancytopenia in early childhood. Patients may have additional variable nonspecific somatic abnormalities, including poor growth, microcephaly, and skin anomalies (summary by Tummala et al., 2016). BMFS3 has a distinct phenotype and may include features that overlap with Shwachman-Diamond syndrome (SDS1; 260400), such as pancreatic insufficiency and short stature, and with dyskeratosis congenita (see, e.g., DKCA1, 127550), such as dental and hair abnormalities and shortened telomeres. In addition, some patients may have joint and skeletal abnormalities, impaired development, and retinal dysplasia (summary by D'Amours et al., 2018). For a discussion of genetic heterogeneity of BMFS, see BMFS1 (614675). (617052) (Updated 20-May-2021)

MalaCards based summary : Bone Marrow Failure Syndrome 3, is also known as bmfs3. An important gene associated with Bone Marrow Failure Syndrome 3 is DNAJC21 (DnaJ Heat Shock Protein Family (Hsp40) Member C21). Affiliated tissues include bone marrow, bone and pancreas, and related phenotypes are microcephaly and hypodontia

UniProtKB/Swiss-Prot : 72 Bone marrow failure syndrome 3: A form of bone marrow failure syndrome, a heterogeneous group of life- threatening disorders characterized by hematopoietic defects in association with a range of variable extra hematopoietic features. BMFS3 is characterized by pancytopenia with onset in early childhood. Some patients have additional variable non-specific features, including poor growth, microcephaly, and skin anomalies. BMFS3 inheritance is autosomal recessive.

Related Diseases for Bone Marrow Failure Syndrome 3

Symptoms & Phenotypes for Bone Marrow Failure Syndrome 3

Human phenotypes related to Bone Marrow Failure Syndrome 3:

31 (show all 40)
# Description HPO Frequency HPO Source Accession
1 microcephaly 31 occasional (7.5%) HP:0000252
2 hypodontia 31 occasional (7.5%) HP:0000668
3 retinal dystrophy 31 occasional (7.5%) HP:0000556
4 acute myeloid leukemia 31 occasional (7.5%) HP:0004808
5 hearing impairment 31 very rare (1%) HP:0000365
6 global developmental delay 31 very rare (1%) HP:0001263
7 hyperactivity 31 very rare (1%) HP:0000752
8 metaphyseal dysplasia 31 very rare (1%) HP:0100255
9 failure to thrive 31 HP:0001508
10 hypertelorism 31 HP:0000316
11 abnormal facial shape 31 HP:0001999
12 short stature 31 HP:0004322
13 hernia 31 HP:0100790
14 hyperkeratosis 31 HP:0000962
15 microdontia 31 HP:0000691
16 reduced bone mineral density 31 HP:0004349
17 cryptorchidism 31 HP:0000028
18 intrauterine growth retardation 31 HP:0001511
19 micrognathia 31 HP:0000347
20 epicanthus 31 HP:0000286
21 myopia 31 HP:0000545
22 exocrine pancreatic insufficiency 31 HP:0001738
23 congenital hip dislocation 31 HP:0001374
24 joint hypermobility 31 HP:0001382
25 downslanted palpebral fissures 31 HP:0000494
26 eczema 31 HP:0000964
27 aplasia/hypoplasia of the eyebrow 31 HP:0100840
28 abnormality of skin pigmentation 31 HP:0001000
29 sparse hair 31 HP:0008070
30 astigmatism 31 HP:0000483
31 recurrent infections 31 HP:0002719
32 cupped ear 31 HP:0000378
33 bone marrow hypocellularity 31 HP:0005528
34 nail dystrophy 31 HP:0008404
35 pancytopenia 31 HP:0001876
36 small nail 31 HP:0001792
37 amelogenesis imperfecta 31 HP:0000705
38 hypermetropia 31 HP:0000540
39 hypoplasia of dental enamel 31 HP:0006297
40 aplastic anemia 31 HP:0001915

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive
intrauterine growth retardation (iugr)

Growth Height:
short stature

Head And Neck Teeth:
microdontia
hypodontia
amelogenesis imperfecta
enamel hypoplasia

Head And Neck Face:
micrognathia
dysmorphic facial features, variable

Skeletal Limbs:
congenital hip dislocation
metaphyseal dysplasia (in some patients)

Skin Nails Hair Hair:
sparse hair

Skin Nails Hair Nails:
nail dystrophy
nail hypoplasia

Muscle Soft Tissue:
hernias

Head And Neck Ears:
cupped ears
hearing impairment, mild (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
eleven pairs of ribs
pectus abnormalities

Neoplasia:
acute myeloid leukemia (1 patient)

Head And Neck Eyes:
hypertelorism
epicanthus
myopia
downslanted palpebral fissures
astigmatism
more
Skin Nails Hair Skin:
hyperkeratosis
eczema
abnormal skin pigmentation

Genitourinary External Genitalia Male:
cryptorchidism

Abdomen Pancreas:
exocrine pancreatic insufficiency
atrophic pancreas

Skeletal:
joint hypermobility
decreased bone mineral density

Immunology:
recurrent infections

Hematology:
pancytopenia
aplastic anemia
bone marrow failure

Head And Neck Head:
microcephaly (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
hyperactivity (in some patients)

Neurologic Central Nervous System:
global developmental delay (in some patients)

Laboratory Abnormalities:
decreased serum pancreatic enzymes (in some patients)
shortened telomeres (in some patients)

Clinical features from OMIM®:

617052 (Updated 20-May-2021)

Drugs & Therapeutics for Bone Marrow Failure Syndrome 3

Search Clinical Trials , NIH Clinical Center for Bone Marrow Failure Syndrome 3

Genetic Tests for Bone Marrow Failure Syndrome 3

Genetic tests related to Bone Marrow Failure Syndrome 3:

# Genetic test Affiliating Genes
1 Bone Marrow Failure Syndrome 3 29 DNAJC21

Anatomical Context for Bone Marrow Failure Syndrome 3

MalaCards organs/tissues related to Bone Marrow Failure Syndrome 3:

40
Bone Marrow, Bone, Pancreas, Myeloid

Publications for Bone Marrow Failure Syndrome 3

Articles related to Bone Marrow Failure Syndrome 3:

# Title Authors PMID Year
1
Refining the phenotype associated with biallelic DNAJC21 mutations. 57 6
29700810 2018
2
Biallelic mutations in DNAJC21 cause Shwachman-Diamond syndrome. 6 57
28062395 2017
3
DNAJC21 Mutations Link a Cancer-Prone Bone Marrow Failure Syndrome to Corruption in 60S Ribosome Subunit Maturation. 6 57
27346687 2016

Variations for Bone Marrow Failure Syndrome 3

ClinVar genetic disease variations for Bone Marrow Failure Syndrome 3:

6 (show all 14)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 DNAJC21 NM_001012339.3(DNAJC21):c.94C>G (p.Pro32Ala) SNV Pathogenic 222063 rs879253818 GRCh37: 5:34930018-34930018
GRCh38: 5:34929913-34929913
2 DNAJC21 NM_001012339.3(DNAJC21):c.517C>T (p.Arg173Ter) SNV Pathogenic 222064 rs150576702 GRCh37: 5:34937509-34937509
GRCh38: 5:34937404-34937404
3 DNAJC21 NM_001012339.3(DNAJC21):c.793G>T (p.Glu265Ter) SNV Pathogenic 222065 rs770282904 GRCh37: 5:34939012-34939012
GRCh38: 5:34938907-34938907
4 DNAJC21 NM_001012339.3(DNAJC21):c.983+1G>T SNV Pathogenic 253171 rs368148362 GRCh37: 5:34941289-34941289
GRCh38: 5:34941184-34941184
5 DNAJC21 NM_001012339.3(DNAJC21):c.520C>T (p.Gln174Ter) SNV Pathogenic 617606 rs1561183139 GRCh37: 5:34937512-34937512
GRCh38: 5:34937407-34937407
6 DNAJC21 NM_001012339.3(DNAJC21):c.100A>G (p.Lys34Glu) SNV Pathogenic 617607 rs1561180439 GRCh37: 5:34933922-34933922
GRCh38: 5:34933817-34933817
7 DNAJC21 NM_001012339.3(DNAJC21):c.1494del (p.Phe498fs) Deletion Pathogenic 998360 GRCh37: 5:34954713-34954713
GRCh38: 5:34954608-34954608
8 DNAJC21 NM_001012339.3(DNAJC21):c.1224dup (p.Gly409fs) Duplication Pathogenic 1028445 GRCh37: 5:34950311-34950312
GRCh38: 5:34950206-34950207
9 DNAJC21 NM_001012339.3(DNAJC21):c.982del (p.Ala328fs) Deletion Pathogenic 802111 rs1580531090 GRCh37: 5:34941286-34941286
GRCh38: 5:34941181-34941181
10 DNAJC21 NM_001012339.3(DNAJC21):c.647_666del (p.Arg216fs) Deletion Pathogenic 807409 rs1580526958 GRCh37: 5:34937635-34937654
GRCh38: 5:34937530-34937549
11 DNAJC21 NM_001012339.3(DNAJC21):c.463T>C (p.Trp155Arg) SNV Uncertain significance 813932 rs1580526653 GRCh37: 5:34937455-34937455
GRCh38: 5:34937350-34937350
12 DNAJC21 NM_001012339.3(DNAJC21):c.1015C>T (p.Arg339Trp) SNV Uncertain significance 1031724 GRCh37: 5:34945003-34945003
GRCh38: 5:34944898-34944898
13 DNAJC21 NM_001012339.3(DNAJC21):c.958G>A (p.Asp320Asn) SNV Uncertain significance 1031725 GRCh37: 5:34941263-34941263
GRCh38: 5:34941158-34941158
14 DNAJC21 NM_001012339.3(DNAJC21):c.983+1G>A SNV Uncertain significance 222066 rs368148362 GRCh37: 5:34941289-34941289
GRCh38: 5:34941184-34941184

UniProtKB/Swiss-Prot genetic disease variations for Bone Marrow Failure Syndrome 3:

72
# Symbol AA change Variation ID SNP ID
1 DNAJC21 p.Pro32Ala VAR_076802 rs879253818

Expression for Bone Marrow Failure Syndrome 3

Search GEO for disease gene expression data for Bone Marrow Failure Syndrome 3.

Pathways for Bone Marrow Failure Syndrome 3

GO Terms for Bone Marrow Failure Syndrome 3

Sources for Bone Marrow Failure Syndrome 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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