BCS1
MCID: BRT028
MIFTS: 33

Brittle Cornea Syndrome 1 (BCS1)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Brittle Cornea Syndrome 1

MalaCards integrated aliases for Brittle Cornea Syndrome 1:

Name: Brittle Cornea Syndrome 1 58 76
Fragilitas Oculi with Joint Hyperextensibility 58 76
Dysgenesis Mesodermalis Corneae Et Sclerae 58 76
Bcs1 58 76
Corneal Fragility, Keratoglobus, Blue Sclerae, Joint Hyperextensibility 58
Corneal Fragility Keratoglobus Blue Sclerae Joint Hyperextensibility 76
Ehlers-Danlos Syndrome, Type Vib, Formerly; Eds6b, Formerly 58
Ehlers-Danlos Syndrome, Type Vib, Formerly 58
Ehlers-Danlos Syndrome Type Vib Formerly 76
Cornea, Brittle, Syndrome, Type 1 41
Ehlers-Danlos Syndrome 6b 74
Eds6b, Formerly 58
Eds6b Formerly 76

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive


HPO:

33
brittle cornea syndrome 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Brittle Cornea Syndrome 1

UniProtKB/Swiss-Prot : 76 Brittle cornea syndrome 1: A disorder characterized by extreme corneal thinning resulting in corneal rupture after minor trauma, blue sclerae, keratoconus or keratoglobus, hyperelasticity of the skin, and hypermobility of the joints. It shares some features with, but is much less severe than, the ocular form of Ehlers-Danlos syndrome (EDS6).

MalaCards based summary : Brittle Cornea Syndrome 1, also known as fragilitas oculi with joint hyperextensibility, is related to ehlers-danlos syndrome, musculocontractural type, 1 and brittle cornea syndrome 2, and has symptoms including unspecified visual loss An important gene associated with Brittle Cornea Syndrome 1 is ZNF469 (Zinc Finger Protein 469). The drugs Folic Acid and Riboflavin have been mentioned in the context of this disorder. Affiliated tissues include skin, liver and bone, and related phenotypes are macrocephaly and scoliosis

OMIM : 58 Brittle cornea syndrome (BCS) is characterized by blue sclerae, corneal rupture after minor trauma, keratoconus or keratoglobus, hyperelasticity of the skin, and hypermobility of the joints (Al-Hussain et al., 2004). It is classified as a form of Ehlers-Danlos syndrome (Malfait et al., 2017). (229200)

Related Diseases for Brittle Cornea Syndrome 1

Diseases in the Brittle Cornea Syndrome 2 family:

Brittle Cornea Syndrome 1

Diseases related to Brittle Cornea Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 ehlers-danlos syndrome, musculocontractural type, 1 11.9
2 brittle cornea syndrome 2 11.2
3 helix syndrome 10.1

Symptoms & Phenotypes for Brittle Cornea Syndrome 1

Human phenotypes related to Brittle Cornea Syndrome 1:

33 (show all 20)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 33 HP:0000256
2 scoliosis 33 HP:0002650
3 hearing impairment 33 HP:0000365
4 dentinogenesis imperfecta 33 HP:0000703
5 epicanthus 33 HP:0000286
6 myopia 33 HP:0000545
7 atypical scarring of skin 33 HP:0000987
8 congenital hip dislocation 33 HP:0001374
9 joint laxity 33 HP:0001388
10 mitral valve prolapse 33 HP:0001634
11 visual loss 33 HP:0000572
12 disproportionate tall stature 33 HP:0001519
13 spondylolisthesis 33 HP:0003302
14 blue sclerae 33 HP:0000592
15 keratoconus 33 HP:0000563
16 keratoglobus 33 HP:0001119
17 palmoplantar cutis laxa 33 HP:0007517
18 decreased corneal thickness 33 HP:0100689
19 red hair 33 HP:0002297
20 molluscoid pseudotumors 33 HP:0000993

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Head:
macrocephaly

Head And Neck Teeth:
dentinogenesis imperfecta

Skeletal Pelvis:
congenital hip dislocation

Cardiovascular Heart:
mitral valve prolapse

Skin Nails Hair Hair:
red hair

Growth Other:
marfanoid habitus

Skeletal Spine:
scoliosis
spondylolisthesis

Head And Neck Eyes:
myopia
blue sclerae
keratoconus
keratoglobus
epicanthal folds
more
Skeletal:
joint laxity

Skin Nails Hair Skin:
scarring
excessive wrinkled skin (palms and soles)
molluscoid pseudotumor

Head And Neck Ears:
hearing loss

Laboratory Abnormalities:
normal lysl hydroxylase activity
normal dermal hydroxylysine content

Clinical features from OMIM:

229200

UMLS symptoms related to Brittle Cornea Syndrome 1:


unspecified visual loss

Drugs & Therapeutics for Brittle Cornea Syndrome 1

Drugs for Brittle Cornea Syndrome 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Folic Acid Approved, Nutraceutical, Vet_approved Not Applicable 59-30-3 6037
2
Riboflavin Approved, Investigational, Nutraceutical, Vet_approved Not Applicable 83-88-5 493570
3 Trace Elements Not Applicable
4 Dermatologic Agents Not Applicable
5 Vitamin B Complex Not Applicable
6 Vitamin B2 Not Applicable
7 Nutrients Not Applicable
8 Folate Not Applicable
9 Vitamins Not Applicable
10 Vitamin B9 Not Applicable
11 Micronutrients Not Applicable
12 Photosensitizing Agents Not Applicable
13 Liver Extracts

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Riboflavin Corneal Crosslinking for Brittle Cornea Syndrome and Ehlers-Danlos Syndrome Type VI Unknown status NCT01307527 Not Applicable Riboflavin
2 The Association With Peptic Ulcer Disease and Hepatic Vein Pressure Gradient Completed NCT01944878

Search NIH Clinical Center for Brittle Cornea Syndrome 1

Genetic Tests for Brittle Cornea Syndrome 1

Anatomical Context for Brittle Cornea Syndrome 1

MalaCards organs/tissues related to Brittle Cornea Syndrome 1:

42
Skin, Liver, Bone, Eye

Publications for Brittle Cornea Syndrome 1

Articles related to Brittle Cornea Syndrome 1:

(show all 16)
# Title Authors Year
1
Chemicals or mutations that target mitochondrial translation can rescue the respiratory deficiency of yeast bcs1 mutants. ( 28888990 )
2017
2
A conserved α helix of Bcs1, a mitochondrial AAA chaperone, is required for the Respiratory Complex III maturation. ( 24361883 )
2014
3
The energetic state of mitochondria modulates complex III biogenesis through the ATP-dependent activity of Bcs1. ( 24055101 )
2013
4
Bcs1, a AAA protein of the mitochondria with a role in the biogenesis of the respiratory chain. ( 22575765 )
2012
5
Late-stage maturation of the Rieske Fe/S protein: Mzm1 stabilizes Rip1 but does not facilitate its translocation by the AAA ATPase Bcs1. ( 22927643 )
2012
6
A pathway of protein translocation in mitochondria mediated by the AAA-ATPase Bcs1. ( 22017868 )
2011
7
Brittle cornea syndrome associated with a missense mutation in the zinc-finger 469 gene. ( 19661234 )
2010
8
Blue sclera with and without corneal fragility (brittle cornea syndrome) in a consanguineous family harboring ZNF469 mutation (p.E1392X). ( 20938016 )
2010
9
Functional analysis of yeast bcs1 mutants highlights the role of Bcs1p-specific amino acids in the AAA domain. ( 19285991 )
2009
10
Deleterious mutations in the Zinc-Finger 469 gene cause brittle cornea syndrome. ( 18452888 )
2008
11
Mitochondrial protein import: recognition of internal import signals of BCS1 by the TOM complex. ( 12640110 )
2003
12
Identification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX15, and COX11, five genes involved in the formation and function of the mitochondrial respiratory chain. ( 9878253 )
1998
13
Internal targeting signal of the BCS1 protein: a novel mechanism of import into mitochondria. ( 8599931 )
1996
14
BCS1, a novel gene required for the expression of functional Rieske iron-sulfur protein in Saccharomyces cerevisiae. ( 1327750 )
1992
15
Brittle cornea, blue sclera, and red hair syndrome (the brittle cornea syndrome). ( 7387950 )
1980
16
Dysgenesis mesodermalis corneae et sclerae. Rupture of both corneae in a patient with blue sclerae. ( 5755738 )
1968

Variations for Brittle Cornea Syndrome 1

ClinVar genetic disease variations for Brittle Cornea Syndrome 1:

6 (show top 50) (show all 612)
# Gene Variation Type Significance SNP ID Assembly Location
1 ZNF469 ZNF469, 1-BP DEL, 5943A deletion Pathogenic
2 ZNF469 ZNF469, 1-BP DEL, 9527G deletion Pathogenic
3 ZNF469 NM_001127464.2(ZNF469): c.10016G> A (p.Cys3339Tyr) single nucleotide variant Pathogenic rs387907062 GRCh37 Chromosome 16, 88503978: 88503978
4 ZNF469 NM_001127464.2(ZNF469): c.10016G> A (p.Cys3339Tyr) single nucleotide variant Pathogenic rs387907062 GRCh38 Chromosome 16, 88437570: 88437570
5 ZNF469 NM_001127464.2(ZNF469): c.4174G> T (p.Glu1392Ter) single nucleotide variant Pathogenic rs387907063 GRCh37 Chromosome 16, 88498136: 88498136
6 ZNF469 NM_001127464.2(ZNF469): c.4174G> T (p.Glu1392Ter) single nucleotide variant Pathogenic rs387907063 GRCh38 Chromosome 16, 88431728: 88431728
7 ZNF469 NM_001127464.2(ZNF469): c.1020C> T (p.Gly340=) single nucleotide variant Conflicting interpretations of pathogenicity rs273585633 GRCh38 Chromosome 16, 88428490: 88428490
8 ZNF469 NM_001127464.2(ZNF469): c.1020C> T (p.Gly340=) single nucleotide variant Conflicting interpretations of pathogenicity rs273585633 GRCh37 Chromosome 16, 88494898: 88494898
9 ZNF469 NM_001127464.2(ZNF469): c.2699C> T (p.Pro900Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs273585618 GRCh38 Chromosome 16, 88430169: 88430169
10 ZNF469 NM_001127464.2(ZNF469): c.2699C> T (p.Pro900Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs273585618 GRCh37 Chromosome 16, 88496577: 88496577
11 ZNF469 NM_001127464.2(ZNF469): c.9471C> G (p.Ala3157=) single nucleotide variant Likely benign rs273585636 GRCh38 Chromosome 16, 88437025: 88437025
12 ZNF469 NM_001127464.2(ZNF469): c.9471C> G (p.Ala3157=) single nucleotide variant Likely benign rs273585636 GRCh37 Chromosome 16, 88503433: 88503433
13 ZNF469 NM_001127464.2(ZNF469): c.1143C> A (p.Pro381=) single nucleotide variant Benign/Likely benign rs74032864 GRCh37 Chromosome 16, 88495021: 88495021
14 ZNF469 NM_001127464.2(ZNF469): c.1143C> A (p.Pro381=) single nucleotide variant Benign/Likely benign rs74032864 GRCh38 Chromosome 16, 88428613: 88428613
15 ZNF469 NM_001127464.2(ZNF469): c.1827G> A (p.Ser609=) single nucleotide variant Conflicting interpretations of pathogenicity rs148616993 GRCh37 Chromosome 16, 88495705: 88495705
16 ZNF469 NM_001127464.2(ZNF469): c.1827G> A (p.Ser609=) single nucleotide variant Conflicting interpretations of pathogenicity rs148616993 GRCh38 Chromosome 16, 88429297: 88429297
17 ZNF469 NM_001127464.2(ZNF469): c.2717C> T (p.Pro906Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs77951481 GRCh37 Chromosome 16, 88496595: 88496595
18 ZNF469 NM_001127464.2(ZNF469): c.2717C> T (p.Pro906Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs77951481 GRCh38 Chromosome 16, 88430187: 88430187
19 ZNF469 NM_001127464.2(ZNF469): c.3153T> C (p.Ile1051=) single nucleotide variant Benign rs9924504 GRCh37 Chromosome 16, 88497031: 88497031
20 ZNF469 NM_001127464.2(ZNF469): c.3153T> C (p.Ile1051=) single nucleotide variant Benign rs9924504 GRCh38 Chromosome 16, 88430623: 88430623
21 ZNF469 NM_001127464.2(ZNF469): c.457C> G (p.Pro153Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs532620482 GRCh37 Chromosome 16, 88494335: 88494335
22 ZNF469 NM_001127464.2(ZNF469): c.457C> G (p.Pro153Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs532620482 GRCh38 Chromosome 16, 88427927: 88427927
23 ZNF469 NM_001127464.2(ZNF469): c.1069T> C (p.Ser357Pro) single nucleotide variant Benign rs11648572 GRCh37 Chromosome 16, 88494947: 88494947
24 ZNF469 NM_001127464.2(ZNF469): c.1069T> C (p.Ser357Pro) single nucleotide variant Benign rs11648572 GRCh38 Chromosome 16, 88428539: 88428539
25 ZNF469 NM_001127464.2(ZNF469): c.1098A> C (p.Arg366Ser) single nucleotide variant Benign rs11640794 GRCh37 Chromosome 16, 88494976: 88494976
26 ZNF469 NM_001127464.2(ZNF469): c.1098A> C (p.Arg366Ser) single nucleotide variant Benign rs11640794 GRCh38 Chromosome 16, 88428568: 88428568
27 ZNF469 NM_001127464.2(ZNF469): c.10891G> A (p.Gly3631Arg) single nucleotide variant Benign/Likely benign rs3812951 GRCh37 Chromosome 16, 88504853: 88504853
28 ZNF469 NM_001127464.2(ZNF469): c.10891G> A (p.Gly3631Arg) single nucleotide variant Benign/Likely benign rs3812951 GRCh38 Chromosome 16, 88438445: 88438445
29 ZNF469 NM_001127464.2(ZNF469): c.10906G= (p.Ala3636=) single nucleotide variant Benign rs904783 GRCh37 Chromosome 16, 88504868: 88504868
30 ZNF469 NM_001127464.2(ZNF469): c.10906G= (p.Ala3636=) single nucleotide variant Benign rs904783 GRCh38 Chromosome 16, 88438460: 88438460
31 ZNF469 NM_001127464.2(ZNF469): c.10242G> C (p.Arg3414Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs56236932 GRCh37 Chromosome 16, 88504204: 88504204
32 ZNF469 NM_001127464.2(ZNF469): c.10242G> C (p.Arg3414Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs56236932 GRCh38 Chromosome 16, 88437796: 88437796
33 ZNF469 NM_001127464.2(ZNF469): c.4868A> G (p.Gln1623Arg) single nucleotide variant Uncertain significance rs773925755 GRCh37 Chromosome 16, 88498830: 88498830
34 ZNF469 NM_001127464.2(ZNF469): c.4868A> G (p.Gln1623Arg) single nucleotide variant Uncertain significance rs773925755 GRCh38 Chromosome 16, 88432422: 88432422
35 ZNF469 NM_001127464.2(ZNF469): c.8543A> G (p.His2848Arg) single nucleotide variant Benign rs1983014 GRCh37 Chromosome 16, 88502505: 88502505
36 ZNF469 NM_001127464.2(ZNF469): c.8543A> G (p.His2848Arg) single nucleotide variant Benign rs1983014 GRCh38 Chromosome 16, 88436097: 88436097
37 ZNF469 NM_001127464.2(ZNF469): c.4337C> T (p.Ala1446Val) single nucleotide variant Benign/Likely benign rs199897247 GRCh37 Chromosome 16, 88498299: 88498299
38 ZNF469 NM_001127464.2(ZNF469): c.4337C> T (p.Ala1446Val) single nucleotide variant Benign/Likely benign rs199897247 GRCh38 Chromosome 16, 88431891: 88431891
39 ZNF469 NM_001127464.2(ZNF469): c.3566C> T (p.Pro1189Leu) single nucleotide variant Benign/Likely benign rs115183769 GRCh37 Chromosome 16, 88497528: 88497528
40 ZNF469 NM_001127464.2(ZNF469): c.3566C> T (p.Pro1189Leu) single nucleotide variant Benign/Likely benign rs115183769 GRCh38 Chromosome 16, 88431120: 88431120
41 ZNF469 NM_001127464.2(ZNF469): c.4259C> T (p.Pro1420Leu) single nucleotide variant Benign rs4782300 GRCh37 Chromosome 16, 88498221: 88498221
42 ZNF469 NM_001127464.2(ZNF469): c.4259C> T (p.Pro1420Leu) single nucleotide variant Benign rs4782300 GRCh38 Chromosome 16, 88431813: 88431813
43 ZNF469 NM_001127464.2(ZNF469): c.7183C> A (p.Pro2395Thr) single nucleotide variant Uncertain significance rs199727372 GRCh37 Chromosome 16, 88501145: 88501145
44 ZNF469 NM_001127464.2(ZNF469): c.7183C> A (p.Pro2395Thr) single nucleotide variant Uncertain significance rs199727372 GRCh38 Chromosome 16, 88434737: 88434737
45 ZNF469 NM_001127464.2(ZNF469): c.4388C> T (p.Thr1463Met) single nucleotide variant Conflicting interpretations of pathogenicity rs375045076 GRCh37 Chromosome 16, 88498350: 88498350
46 ZNF469 NM_001127464.2(ZNF469): c.4388C> T (p.Thr1463Met) single nucleotide variant Conflicting interpretations of pathogenicity rs375045076 GRCh38 Chromosome 16, 88431942: 88431942
47 ZNF469 NM_001127464.2(ZNF469): c.1285G> A (p.Ala429Thr) single nucleotide variant Benign/Likely benign rs113937803 GRCh37 Chromosome 16, 88495163: 88495163
48 ZNF469 NM_001127464.2(ZNF469): c.1285G> A (p.Ala429Thr) single nucleotide variant Benign/Likely benign rs113937803 GRCh38 Chromosome 16, 88428755: 88428755
49 ZNF469 NM_001127464.2(ZNF469): c.2270T> G (p.Leu757Arg) single nucleotide variant Uncertain significance rs753664726 GRCh37 Chromosome 16, 88496148: 88496148
50 ZNF469 NM_001127464.2(ZNF469): c.2270T> G (p.Leu757Arg) single nucleotide variant Uncertain significance rs753664726 GRCh38 Chromosome 16, 88429740: 88429740

Expression for Brittle Cornea Syndrome 1

Search GEO for disease gene expression data for Brittle Cornea Syndrome 1.

Pathways for Brittle Cornea Syndrome 1

GO Terms for Brittle Cornea Syndrome 1

Sources for Brittle Cornea Syndrome 1

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