Björnstad Syndrome: Disease-Characteristics Research Report

Scope and evidence date. This report distinguishes classic Björnstad syndrome—pili torti with sensorineural hearing loss—from severe multisystem BCS1L-related complex III disease. Evidence for the classic syndrome remains limited to small pedigrees and case reports; consequently, percentages, penetrance estimates, survival curves, and treatment-response rates generally cannot be calculated reliably.

Executive summary

Björnstad syndrome is an extremely rare, autosomal-recessive mitochondrial disorder caused by biallelic germline variants in BCS1L. Its defining manifestations are congenital or early-childhood bilateral sensorineural hearing loss and pili torti, a hair-shaft defect in which flattened shafts twist approximately 180° at irregular intervals. Open Targets identifies BCS1L as the only associated target for Björnstad syndrome, MONDO:0009872. Classic disease is usually limited to hair and hearing and is considered the mild end of the BCS1L phenotypic spectrum; renal, hepatic, neurologic, cardiac, or severe metabolic involvement should prompt classification as broader BCS1L-related mitochondrial disease rather than uncomplicated Björnstad syndrome. (OpenTargets Search: Bjornstad syndrome-BCS1L, hinson2007missensemutationsin pages 1-2, tegelberg2017respiratorychaincomplex pages 1-2)

The major recent advance is mechanistic rather than therapeutic. A May 2024 cryo-EM study showed that the BCS1L heptamer uses a concerted ATPase cycle to translocate folded Rieske iron–sulfur protein during late respiratory-complex-III assembly. A July 2024 review confirms that BCS1L variants are the most frequent nuclear genetic cause of complex III deficiency. No approved disease-modifying therapy or Björnstad-specific interventional trial was identified. (zhan2024conformationsofbcs1l pages 1-2, cunatova2024pathologicalvariantsin pages 1-4, cunatova2024pathologicalvariantsin pages 5-7)

The following table provides a compact knowledge-base mapping; the narrative afterward expands the principal fields.

Table: Concise knowledge-base mapping of classic Björnstad syndrome, with explicit separation from severe BCS1L-related complex III disease. It integrates clinical, genetic, mechanistic, ontology, diagnostic and management fields while highlighting 2024 structural advances and evidence gaps.

1. Disease information

Definition and identifiers

• Preferred name: Björnstad syndrome; ASCII form, Bjornstad syndrome.
• Synonyms: pili torti–sensorineural hearing loss syndrome; BCS1L-related Björnstad syndrome; BJS.
• MONDO: MONDO:0009872.
• OMIM: the classic phenotype is commonly indexed as #262000. Some papers report #603647, but that number refers to the BCS1L gene entry; databases should not silently merge the gene and phenotype records. (OpenTargets Search: Bjornstad syndrome-BCS1L, siddiqi2013novelmutationin pages 1-2, blazquez2013mitochondrialcomplexiii pages 7-10)
• Gene: BCS1L, approved name “BCS1 ubiquinol-cytochrome c reductase complex chaperone”; Ensembl ENSG00000074582. (OpenTargets Search: Bjornstad syndrome-BCS1L)
• Orphanet/ICD/MeSH: no dedicated Orphanet, ICD-10, ICD-11, or MeSH identifier was established from the retrieved evidence. An implementation should preserve this as “not verified,” rather than assigning a nonspecific deafness or mitochondrial-disease code as an exact equivalent.

The evidence summarized here is aggregated disease-level literature and database evidence, not individual EHR data. Patient-level observations come from published pedigrees and case reports.

Landmark source

Hinson et al., New England Journal of Medicine, published 22 February 2007, established recessive BCS1L variants as causal and performed human cellular functional studies (PMID 17314340; DOI/URL: https://doi.org/10.1056/NEJMoa055262). The study describes congenital, variably severe sensorineural hearing loss and childhood-recognized pili torti. (OpenTargets Search: Bjornstad syndrome-BCS1L, hinson2007missensemutationsin pages 1-2)

2. Etiology and risk architecture

The primary cause is genetic: two clinically significant germline BCS1L alleles in trans. BCS1L is nuclear encoded; Björnstad syndrome is not caused by an mtDNA variant. In consanguineous families, homozygous alleles are more likely, but consanguinity is not required. Examples include a homozygous p.Tyr301Asn pedigree and compound-heterozygous p.Asp217His/p.Arg224His disease. (siddiqi2013novelmutationin pages 1-2, trinh2021alopeciaandhearing pages 1-2)

For two heterozygous carrier parents, the expected risk per pregnancy is 25% affected, 50% carrier, and 25% unaffected/non-carrier. Published observations support variable expressivity, especially in hearing severity, but robust penetrance estimates are unavailable. No validated susceptibility loci, modifier genes, protective alleles, anticipation, or disease-relevant epigenetic mechanism were identified.

No environmental toxin, lifestyle exposure, infectious agent, or gene–environment interaction is established as a cause. Avoiding traction, heat, bleaching, and harsh chemical treatment may reduce breakage of already fragile hair, but it does not modify the mitochondrial lesion. Diet, smoking, alcohol, exercise, vaccination, and occupational exposure have no demonstrated effect on occurrence of the Mendelian disorder.

3. Phenotypes and temporal development

Core phenotype

1. Sensorineural hearing impairment is usually congenital or recognized in infancy/early childhood, is generally bilateral and cochlear, and ranges from moderate to profound. It may progress. In one five-person Pakistani pedigree, thresholds were 70–110 dB; children had moderate-to-severe loss and adults severe-to-profound loss. Suggested terms include HP:0000407 Sensorineural hearing impairment, bilateral hearing impairment, congenital hearing impairment, and progressive hearing impairment. (siddiqi2013novelmutationin pages 1-2)
2. Pili torti is a physical hair-shaft sign: shafts are flattened and rotated approximately 180° at irregular intervals, causing coarse, dull, brittle hair, hypotrichosis, or nonscarring alopecia. In one pedigree scalp hair and eyelashes began falling out at 2–3 months. Suggested terms are Pili torti, brittle hair, sparse scalp hair/hypotrichosis, and nonscarring alopecia. (siddiqi2013novelmutationin pages 1-2, trinh2021alopeciaandhearing pages 1-2)

Published cases demonstrate variability. A six-year-old had hair shedding and hearing loss by age one, profound cochlear loss, intellectual disability, and normal eyebrows, eyelashes, skin, nails, and testes. By contrast, the five-person pedigree included eyelash loss, anhidrosis, light eyes, short stature, and lean habitus in affected males, with normal teeth, nails, palms, and soles. These secondary features should be coded as case-level observations, not mandatory syndrome criteria. (siddiqi2013novelmutationin pages 1-2, trinh2021alopeciaandhearing pages 1-2)

Course and quality of life

The disorder is chronic and lifelong. Hearing impairment can substantially affect speech and language acquisition, education, social participation, and employment, particularly when intervention is delayed. Hair fragility is not generally medically dangerous but may produce cosmetic and psychosocial burden. No Björnstad-specific EQ-5D, SF-36, PROMIS, or longitudinal natural-history dataset was found.

There are no validated clinical stages or remission pattern. Hair density and hearing severity may vary, but spontaneous molecular remission is not expected. Infancy and early childhood constitute the critical intervention window for hearing habilitation and language development.

4. Genetics and pathogenic variants

BCS1L encodes a 419-amino-acid, inner-mitochondrial-membrane AAA-family ATPase/chaperone. Its architecture comprises an N-terminal mitochondrial targeting/transmembrane region, a Bcs1-specific middle domain, and a C-terminal AAA ATPase domain. (hinson2007missensemutationsin pages 1-2, zhan2024conformationsofbcs1l pages 2-3, blazquez2013mitochondrialcomplexiii pages 7-10)

Representative classic-associated variants include:

• c.901T>A, p.Tyr301Asn, homozygous, exon 8/AAA domain. It segregated with disease in five relatives, was absent from 137 Pakistani controls and 1000 Genomes, and was computationally predicted deleterious. Published 31 October 2013; DOI: https://doi.org/10.1038/jhg.2013.101. (siddiqi2013novelmutationin pages 1-2)
• c.649G>C, p.Asp217His and c.671G>A, p.Arg224His, compound heterozygous; each unaffected parent carried one allele. The former was novel in the 2021 report; the latter was previously observed at very low population frequency. DOI: https://doi.org/10.1111/pde.14768. (trinh2021alopeciaandhearing pages 1-2)

Broader-spectrum examples must not automatically be annotated as classic Björnstad alleles: homozygous c.142A>G, p.Met48Val caused deafness with Fanconi-type tubulopathy, growth retardation, microcephaly, and liver dysfunction; homozygous c.712A>G, p.Ser328Gly was associated with severe neonatal multisystem disease; and c.548G>A, p.Arg183His plus c.1061_1062insCTA, p.Gly354delinsGlyTyr occurred with complex III deficiency and neurologic, renal, hepatic, and metabolic manifestations. (qurashi2022clinicalanddiagnostic pages 1-2, jackson2016anovelmutation pages 1-2)

Published labels such as “novel,” “predicted pathogenic,” or “disease-associated” should not substitute for current ACMG/AMP assessment. A production database should retrieve current ClinVar assertions, gnomAD allele counts, transcript version, segregation, and functional evidence for each exact allele. The retrieved literature did not provide reliable current frequencies for every variant. No recurrent chromosomal abnormality, pathogenic aneuploidy, somatic origin, methylation signature, or repeat expansion is implicated.

5–6. Pathophysiology and current mechanistic understanding

Ordered causal chain

1. Biallelic BCS1L dysfunction leads to impaired function or organization of the mitochondrial inner-membrane BCS1L ATPase complex.
2. Impaired BCS1L leads to defective ATP-dependent translocation of the folded, Fe–S-cluster-containing UQCRFS1/Rieske ISP extrinsic domain from the matrix side across the inner membrane.
3. Defective translocation/insertion results in accumulation of Rieske-deficient complex III precomplexes and impaired final maturation of dimeric complex III.
4. Defective complex III assembly leads to reduced ubiquinol-to-cytochrome-c electron transport, altered proton translocation, impaired respirasome/oxidative-phosphorylation performance, and altered reactive-oxygen-species handling. (hinson2007missensemutationsin pages 1-2, tegelberg2017respiratorychaincomplex pages 1-2, cunatova2024pathologicalvariantsin pages 1-4)
5. Energetic/redox stress is inferred to cause selective dysfunction or injury of cochlear sensory cells and hair-follicle cells; direct human cell-type-resolved proof remains incomplete.
6. Cochlear dysfunction results in sensorineural hearing loss, while hair-follicle/hair-shaft dysfunction results in pili torti, fragility, and hypotrichosis.
7. Branch: more disruptive alleles—especially those affecting ATP binding/hydrolysis—can lead to systemic respiratory-chain failure, causing lactic acidosis, renal tubulopathy, hepatopathy, encephalopathy, cardiomyopathy, or GRACILE syndrome rather than classic restricted Björnstad syndrome. (hinson2007missensemutationsin pages 9-10, cunatova2024pathologicalvariantsin pages 5-7)

Hinson et al. found disrupted complex III/respirasome assembly, reduced electron-transport activity, and increased ROS in variant-bearing cells. Björnstad-associated substitutions tended to map to externally exposed residues implicated in protein interactions, whereas severe alleles more directly affected ATP binding/hydrolysis. Complex I-derived superoxide was higher in severe complex-III mutations than in Björnstad mutations (P=0.04), supporting—but not proving—the proposed severity gradient. (hinson2007missensemutationsin pages 1-2, hinson2007missensemutationsin pages 9-10)

2024 structural update

Zhan et al., Nature Communications, accepted 20 May 2024, used cryo-EM during active ATP hydrolysis. Their abstract states: “The human AAA-ATPase Bcs1L translocates the fully assembled Rieske iron-sulfur protein (ISP) precursor across the mitochondrial inner membrane, enabling respiratory Complex III assembly.” The subunits moved directly and uniformly between ATP- and ADP-associated conformations without detectable mixed nucleotide intermediates, favoring a concerted, rather than sequential staircase/threading, mechanism. Folded ISP could be trapped in the all-ADP state and was proposed to be released in the apo state; purified ISP stimulated ATPase activity by approximately 50%. DOI/URL: https://doi.org/10.1038/s41467-024-49029-y. (zhan2024conformationsofbcs1l pages 1-2, zhan2024conformationsofbcs1l pages 2-3)

The 2024 complex III review states: “Mitochondrial disorders are a group of clinically and biochemically heterogeneous genetic diseases within the group of inborn errors of metabolism.” It places BCS1L at the final UQCRFS1 insertion/activation step and identifies BCS1L variants as the most frequent among nuclear causes of complex III deficiency. Čunátová and Fernández-Vizarra, accepted 2 May 2024, published July 2024; DOI/URL: https://doi.org/10.1002/jimd.12751. (cunatova2024pathologicalvariantsin pages 1-4, cunatova2024pathologicalvariantsin pages 5-7)

Suggested ontology annotations

• GO biological process: mitochondrial respiratory-chain complex III assembly; protein translocation across mitochondrial inner membrane; ubiquinol-to-cytochrome-c electron transport; oxidative phosphorylation; proton transmembrane transport; cellular response to oxidative stress.
• GO cellular component: GO:0005743 mitochondrial inner membrane; mitochondrial matrix; GO:0005750 mitochondrial respiratory-chain complex III; GO:0070469 respirasome.
• Cell Ontology: auditory hair cell; inner hair cell; outer hair cell; hair-follicle keratinocyte. These cell assignments are biologically plausible but not all are directly established by single-cell analysis in patients.
• No Björnstad-specific transcriptomic, proteomic, metabolomic, lipidomic, single-cell, spatial-transcriptomic, epigenomic, or multi-omic diagnostic signature was identified.

7. Anatomical structures affected

The principal organs/tissues are the inner ear/cochlea, especially the auditory sensory apparatus, and scalp hair follicles/hair shafts. Suggested UBERON concepts are cochlea, organ of Corti, inner ear, skin of scalp, and hair follicle. Hearing loss is generally bilateral. Hair involvement is principally scalp hair; eyebrow, eyelash, and other body-hair involvement is variable. (siddiqi2013novelmutationin pages 1-2, trinh2021alopeciaandhearing pages 1-2)

Renal tubules, liver, brain, skeletal muscle, and heart are secondary sites in broader BCS1L mitopathy, not required anatomical targets in classic Björnstad syndrome. A patient with p.Met48Val showed muscle-specific complex III deficiency absent in fibroblasts, illustrating tissue dependence of biochemical testing. (jackson2016anovelmutation pages 1-2)

8–9. Natural history, inheritance, and population

Onset is congenital to early pediatric and generally insidious rather than acute. Hearing impairment may progress; pili torti and hair fragility are usually apparent in infancy or childhood. Classic disease is lifelong and generally considered compatible with normal lifespan, whereas severe BCS1L-related disease can cause early death. (siddiqi2013novelmutationin pages 1-2, blazquez2013mitochondrialcomplexiii pages 7-10, cunatova2024pathologicalvariantsin pages 5-7)

No credible prevalence per 100,000, incidence, carrier frequency, or sex ratio was identified. Both males and females are affected, as expected for autosomal-recessive inheritance. Reports include families from multiple geographic ancestries. Consanguinity has facilitated discovery of homozygous alleles, but no classic Björnstad founder effect was established. There is no evidence of genetic anticipation. Published case counts should not be converted into prevalence because ascertainment and publication bias are severe.

10. Diagnostics

Recommended workflow

1. Phenotype recognition: early bilateral sensorineural hearing loss plus sparse, brittle, or lusterless scalp hair.
2. Audiology: age-appropriate pure-tone or behavioral audiometry, auditory brainstem response, otoacoustic emissions, tympanometry, and speech testing to define cochlear versus conductive/retrocochlear disease and quantify severity.
3. Hair examination: trichoscopy followed by light or electron microscopy when needed. Pili torti is flattened hair with irregular approximately 180° twists; it is a sign, not a disease-specific test. (trinh2021alopeciaandhearing pages 1-2)
4. Molecular confirmation: sequencing and deletion/duplication analysis of BCS1L, or a syndromic-hearing-loss/mitochondrial panel. Demonstrating two clinically significant variants in trans and parental segregation is preferred.
5. Expanded testing: WES or WGS is useful when targeted testing is negative, the phenotype is atypical, or additional organ involvement suggests another mitochondrial diagnosis. RNA studies may help resolve splice variants, but no validated Björnstad transcriptomic assay exists.
6. Biochemical support: lactate, liver and renal indices, respiratory-chain enzyme assays, oxygen-consumption studies, blue-native PAGE, and complex III assembly analysis may be indicated in multisystem disease or variant functional assessment. Routine spectrophotometric assays and fibroblasts can miss tissue-dependent complex III abnormalities. (tegelberg2017respiratorychaincomplex pages 1-2, jackson2016anovelmutation pages 1-2)

CMA, karyotyping, FISH, mitochondrial-genome sequencing, and repeat-expansion testing are not first-line tests for a classic phenotype unless independent features indicate them. No circulating biomarker, metabolite, pathology criterion, or imaging finding is diagnostic.

Differential diagnosis

Important alternatives include Crandall syndrome—pili torti and hearing loss with hypogonadism—Menkes disease, isolated pili torti, Netherton syndrome, ectodermal dysplasias, and acquired pili torti associated with inflammatory alopecias, malnutrition, systemic disease, or medications. Broader metabolic findings require consideration of GRACILE syndrome, other BCS1L mitopathies, and defects of other complex III assembly genes. (trinh2021alopeciaandhearing pages 1-2)

11. Outcome and prognosis

No 5- or 10-year survival statistics, disease-specific mortality rates, or validated prognostic biomarkers exist for classic Björnstad syndrome. Available literature describes it as the mildest BCS1L phenotype and generally compatible with normal lifespan. Principal morbidity is permanent hearing disability and its developmental consequences; hair fragility is lifelong but not ordinarily life-threatening. (blazquez2013mitochondrialcomplexiii pages 7-10)

Prognosis changes materially when lactic acidosis, failure to thrive, tubulopathy, hepatic dysfunction, encephalopathy, seizures, cardiomyopathy, or profound developmental abnormalities are present. Such patients occupy the broader BCS1L disease spectrum, where early mortality can occur, and should not be counseled using classic Björnstad expectations. (qurashi2022clinicalanddiagnostic pages 1-2, jackson2016anovelmutation pages 1-2, cunatova2024pathologicalvariantsin pages 5-7)

12. Treatment and real-world implementation

There is no curative or approved BCS1L-directed pharmacotherapy, gene therapy, RNA therapy, cell therapy, or precision small-molecule treatment.

• Hearing: prompt hearing-aid fitting, serial audiology, speech/language therapy, educational accommodations, and communication support. Cochlear implantation is reasonable for severe-to-profound loss when conventional audiological criteria are met, although the retrieved evidence did not provide extractable numerical outcome data from the 2024 case series. Suggested NCIT concepts: Hearing Aid Device, Cochlear Implantation, Speech Therapy, Audiologic Rehabilitation.
• Hair: gentle grooming, avoidance of heat/chemical trauma and traction, cosmetic camouflage, and dermatologic support. Evidence for pharmacologic hair-growth treatment is insufficient.
• Broader disease: mitochondrial-specialist care and organ-specific management for renal, hepatic, neurologic, cardiac, nutritional, and metabolic complications.

A 2020 multisystem case used CoQ10, carnitine, and vitamins alongside seizure therapy and reported short-term clinical improvement, but this is uncontrolled anecdotal evidence from complex III deficiency—not proof of efficacy in classic Björnstad syndrome. Vitamin or “mitochondrial cocktail” therapy should therefore not be represented as established treatment. (qurashi2022clinicalanddiagnostic pages 1-2)

No Björnstad-specific ClinicalTrials.gov interventional study was identified. Pharmacogenomic recommendations, treatment-response rates, and syndrome-specific adverse-event statistics are unavailable.

13. Prevention

Primary prevention by lifestyle, vaccination, or environmental modification is not applicable to a recessive germline disorder. Clinically meaningful prevention focuses on recurrence and complications:

• genetic counseling and confirmation of familial variants;
• cascade carrier testing for adult relatives;
• prenatal molecular diagnosis or PGT-M when familial pathogenic/likely pathogenic variants are known;
• prompt newborn/infant hearing assessment in at-risk children;
• early hearing habilitation to reduce language and educational consequences;
• avoidance of unnecessary hair trauma to reduce breakage.

Population newborn molecular screening is not established. Vaccination, antimicrobial prophylaxis, and public-health environmental controls are not disease-specific interventions.

14–15. Other species and model organisms

No naturally occurring veterinary equivalent, breed association, zoonotic potential, or cross-species transmission is known. BCS1L orthologues are evolutionarily conserved, but Björnstad syndrome is not infectious.

Saccharomyces cerevisiae Bcs1 has been central to defining ATP-dependent insertion/translocation of folded Rieske protein and can be used for variant validation and phenotype-based drug screening. Mammalian Bcs1l knock-in/mutant mice reproduce aspects of broader complex III deficiency, hepatopathy, and tissue macrophage abnormalities. A 2017 mouse model partially phenocopied encephalomyopathic BCS1L disease, including abnormalities of microglia and Kupffer cells; it was not a validated model of the classic hair-plus-hearing syndrome. (tegelberg2017respiratorychaincomplex pages 1-2, blazquez2013mitochondrialcomplexiii pages 7-10)

No model was identified that robustly reproduces both human pili torti and progressive sensorineural hearing loss from a classic Björnstad allele. This limits preclinical evaluation of tissue-selective therapies.

Evidence assessment and key gaps

The strongest causal evidence combines recessive segregation, absence/rarity in controls, human cell functional assays, and conserved structural biology. However, the clinical evidence base remains dominated by individual cases and small consanguineous pedigrees. Frequencies of secondary phenotypes, penetrance, progression rates, quality-of-life scores, carrier frequencies, and intervention outcomes are therefore unknown rather than zero.

The central unresolved question is why partial disruption of a ubiquitous respiratory-chain assembly factor preferentially injures cochlear and hair-follicle tissues in classic disease. No validated modifier gene, protective variant, environmental interaction, epigenetic signature, omics biomarker, prognostic model, classic animal model, or disease-modifying trial was found. The 2024 structural studies clarify the normal ATP-driven machine and create a framework for interpreting variants, but they do not yet supply a therapy. (hinson2007missensemutationsin pages 9-10, trinh2021alopeciaandhearing pages 2-2, zhan2024conformationsofbcs1l pages 1-2, cunatova2024pathologicalvariantsin pages 5-7)

Selected primary and authoritative references

1. Hinson JT et al. Missense mutations in the BCS1L gene as a cause of the Björnstad syndrome. N Engl J Med. 2007;356:809–819. Published 22 February 2007. PMID: 17314340. https://doi.org/10.1056/NEJMoa055262. (hinson2007missensemutationsin pages 1-2)
2. Siddiqi S et al. Novel mutation in AAA domain of BCS1L causing Bjornstad syndrome. J Hum Genet. 2013;58:819–821. Published 31 October 2013. https://doi.org/10.1038/jhg.2013.101. (siddiqi2013novelmutationin pages 1-2)
3. Trinh NB et al. Alopecia and hearing loss in a boy. Pediatr Dermatol. 2021;38:e61–e62. Published November 2021. https://doi.org/10.1111/pde.14768. (trinh2021alopeciaandhearing pages 1-2)
4. Tegelberg S et al. Respiratory chain complex III deficiency due to mutated BCS1L: a novel phenotype with encephalomyopathy, partially phenocopied in a Bcs1l mutant mouse model. Orphanet J Rare Dis. 2017;12:73. https://doi.org/10.1186/s13023-017-0624-2. (tegelberg2017respiratorychaincomplex pages 1-2)
5. Zhan J et al. Conformations of Bcs1L undergoing ATP hydrolysis suggest a concerted translocation mechanism for folded iron-sulfur protein substrate. Nat Commun. 2024;15. Published May 2024. https://doi.org/10.1038/s41467-024-49029-y. (zhan2024conformationsofbcs1l pages 1-2)
6. Čunátová K, Fernández-Vizarra E. Pathological variants in nuclear genes causing mitochondrial complex III deficiency: An update. J Inherit Metab Dis. 2024;47:1278–1291. Published July 2024. https://doi.org/10.1002/jimd.12751. (cunatova2024pathologicalvariantsin pages 1-4, cunatova2024pathologicalvariantsin pages 5-7)

References

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2. (hinson2007missensemutationsin pages 1-2): J. Travis Hinson, Valeria R. Fantin, Jost Schönberger, Noralv Breivik, Geir Siem, Barbara McDonough, Pankaj Sharma, Ivan Keogh, Ricardo Godinho, Felipe Santos, Alfonso Esparza, Yamileth Nicolau, Edgar Selvaag, Bruce H. Cohen, Charles L. Hoppel, Lisbeth Tranebjærg, Roland D. Eavey, J.G. Seidman, and Christine E. Seidman. Missense mutations in the bcs1l gene as a cause of the björnstad syndrome. The New England journal of medicine, 356 8:809-19, Feb 2007. URL: https://doi.org/10.1056/nejmoa055262, doi:10.1056/nejmoa055262. This article has 253 citations and is from a highest quality peer-reviewed journal.

3. (tegelberg2017respiratorychaincomplex pages 1-2): Saara Tegelberg, Nikica Tomašić, Jukka Kallijärvi, Janne Purhonen, Eskil Elmér, Eva Lindberg, David Gisselsson Nord, Maria Soller, Nicole Lesko, Anna Wedell, Helene Bruhn, Christoph Freyer, Henrik Stranneheim, Rolf Wibom, Inger Nennesmo, Anna Wredenberg, Erik A. Eklund, and Vineta Fellman. Respiratory chain complex iii deficiency due to mutated bcs1l: a novel phenotype with encephalomyopathy, partially phenocopied in a bcs1l mutant mouse model. Orphanet Journal of Rare Diseases, Apr 2017. URL: https://doi.org/10.1186/s13023-017-0624-2, doi:10.1186/s13023-017-0624-2. This article has 32 citations and is from a peer-reviewed journal.

4. (zhan2024conformationsofbcs1l pages 1-2): Jingyu Zhan, Allison R. Zeher, Rick Huang, Wai Kwan Tang, Lisa M. Jenkins, and Di Xia. Conformations of bcs1l undergoing atp hydrolysis suggest a concerted translocation mechanism for folded iron-sulfur protein substrate. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-49029-y, doi:10.1038/s41467-024-49029-y. This article has 14 citations and is from a highest quality peer-reviewed journal.

5. (cunatova2024pathologicalvariantsin pages 1-4): Kristýna Čunátová and Erika Fernández‐Vizarra. Pathological variants in nuclear genes causing mitochondrial complex iii deficiency: an update. Journal of Inherited Metabolic Disease, 47:1278-1291, Jul 2024. URL: https://doi.org/10.1002/jimd.12751, doi:10.1002/jimd.12751. This article has 19 citations and is from a peer-reviewed journal.

6. (cunatova2024pathologicalvariantsin pages 5-7): Kristýna Čunátová and Erika Fernández‐Vizarra. Pathological variants in nuclear genes causing mitochondrial complex iii deficiency: an update. Journal of Inherited Metabolic Disease, 47:1278-1291, Jul 2024. URL: https://doi.org/10.1002/jimd.12751, doi:10.1002/jimd.12751. This article has 19 citations and is from a peer-reviewed journal.

7. (blazquez2013mitochondrialcomplexiii pages 7-10): Alberto Blázquez, Lorena Marín-Buera, María Morán, Alberto García-Bartolomé, Joaquín Arenas, Miguel A. Martín, and Cristina Ugalde. Mitochondrial complex iii deficiency of nuclear origin. ArXiv, pages 219-238, Sep 2013. URL: https://doi.org/10.1007/978-1-4614-3722-2_14, doi:10.1007/978-1-4614-3722-2_14. This article has 0 citations.

8. (siddiqi2013novelmutationin pages 1-2): Saima Siddiqi, Saadat Siddiq, Atika Mansoor, Jaap Oostrik, Nafees Ahmad, Syed Ali Raza Kazmi, Hannie Kremer, Raheel Qamar, and Margit Schraders. Novel mutation in aaa domain of bcs1l causing bjornstad syndrome. Journal of Human Genetics, 58:819-821, Oct 2013. URL: https://doi.org/10.1038/jhg.2013.101, doi:10.1038/jhg.2013.101. This article has 26 citations and is from a peer-reviewed journal.

9. (trinh2021alopeciaandhearing pages 1-2): Ngo Binh Trinh, Hoang Anh Vu, Anh Khoa Pham, Waleed Adawi, Stephanie A. Castillo, and Linh Ngoc Tuong Tran. Alopecia and hearing loss in a boy. Pediatric Dermatology, Nov 2021. URL: https://doi.org/10.1111/pde.14768, doi:10.1111/pde.14768. This article has 1 citations and is from a peer-reviewed journal.

10. (zhan2024conformationsofbcs1l pages 2-3): Jingyu Zhan, Allison R. Zeher, Rick Huang, Wai Kwan Tang, Lisa M. Jenkins, and Di Xia. Conformations of bcs1l undergoing atp hydrolysis suggest a concerted translocation mechanism for folded iron-sulfur protein substrate. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-49029-y, doi:10.1038/s41467-024-49029-y. This article has 14 citations and is from a highest quality peer-reviewed journal.

11. (qurashi2022clinicalanddiagnostic pages 1-2): Mansour Al Qurashi, Ahmed Mustafa, Syed Sameer Aga, Abrar Ahmad, Abdellatif El-Farra, Aiman Shawli, Mohammed Al Hindi, and Mohammed Hasosah. Clinical and diagnostic characteristics of complex iii mitopathy due to novel bcs1l gene mutation in a saudi patient. BMC Medical Genomics, Mar 2022. URL: https://doi.org/10.1186/s12920-022-01210-2, doi:10.1186/s12920-022-01210-2. This article has 3 citations and is from a peer-reviewed journal.

12. (jackson2016anovelmutation pages 1-2): C. B. Jackson, M. F. Bauer, A. Schaller, U. Kotzaeridou, A. Ferrarini, D. Hahn, H. Chehade, F. Barbey, C. Tran, S. Gallati, A. Haeberli, S. Eggimann, L. Bonafé, and J-M. Nuoffer. A novel mutation in bcs1l associated with deafness, tubulopathy, growth retardation and microcephaly. European Journal of Pediatrics, 175:517-525, Apr 2016. URL: https://doi.org/10.1007/s00431-015-2661-y, doi:10.1007/s00431-015-2661-y. This article has 24 citations and is from a peer-reviewed journal.

13. (hinson2007missensemutationsin pages 9-10): J. Travis Hinson, Valeria R. Fantin, Jost Schönberger, Noralv Breivik, Geir Siem, Barbara McDonough, Pankaj Sharma, Ivan Keogh, Ricardo Godinho, Felipe Santos, Alfonso Esparza, Yamileth Nicolau, Edgar Selvaag, Bruce H. Cohen, Charles L. Hoppel, Lisbeth Tranebjærg, Roland D. Eavey, J.G. Seidman, and Christine E. Seidman. Missense mutations in the bcs1l gene as a cause of the björnstad syndrome. The New England journal of medicine, 356 8:809-19, Feb 2007. URL: https://doi.org/10.1056/nejmoa055262, doi:10.1056/nejmoa055262. This article has 253 citations and is from a highest quality peer-reviewed journal.

14. (trinh2021alopeciaandhearing pages 2-2): Ngo Binh Trinh, Hoang Anh Vu, Anh Khoa Pham, Waleed Adawi, Stephanie A. Castillo, and Linh Ngoc Tuong Tran. Alopecia and hearing loss in a boy. Pediatric Dermatology, Nov 2021. URL: https://doi.org/10.1111/pde.14768, doi:10.1111/pde.14768. This article has 1 citations and is from a peer-reviewed journal.

Artifacts

• Edison artifact artifact-00

Reference Validation

Checked with linkml-reference-validator 0.2.1.

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Obsolete terms

These terms are real but deprecated. Citing one is not a fabrication; it does mean the report is naming something the ontology has retired:

• GO:0005750 (obsolete mitochondrial respiratory chain complex III) (2 mentions) - replaced by GO:0045275
• GO:0070469 (obsolete respirasome) (2 mentions) - replaced by GO:0098803

3 of 5 terms resolved to a current term; the rest could not be looked up either way.