Let me fetch the primary papers' abstracts from PubMed.

I'm reading the cached full text of the 2018 index paper (Iuso et al.) for clinical and functional detail. Next I'll fetch the 2025 pantethine study and the 2022 iPSC paper.

I have the clinical case series from the 2025 paper. Now I'm reading its iPSC-cardiomyocyte and pantethine results, then I'll write the report.

I've finished reading the primary literature and checking ontology terms against the repo caches. Writing the report now.

Cardiomyopathy, Dilated, 2C (CMD2C): PPCS deficiency disorder

Scope and sourcing. There are only three disease-specific primary papers and one cell-line report. Their abstracts and full texts were cached with just fetch-reference:

All quotes below come from these cached files. Any ontology ID marked ✔ was found in this repo's cache/*/terms.csv with the label shown. Any ID marked ⚠ was not found in the cache and must be looked up before you bind it.

1. Disease information

Overview. CMD2C is an ultra-rare autosomal recessive cardiomyopathy. It is caused by biallelic hypomorphic variants in PPCS, which encodes the second enzyme of de novo coenzyme A (CoA) biosynthesis from vitamin B5. The 2025 paper names the condition "PPCS deficiency disorder (PPCS DD)" and defines it as follows:

"PPCS deficiency disorder (PPCS DD) is an ultra-rare, autosomal recessive form of dilated cardiomyopathy (DCM) caused by pathogenic variants in PPCS, which encodes the enzyme catalyzing the second step in the coenzyme A (CoA) biosynthesis pathway." (PMID:40745475)

The 2018 index paper describes it as cardiac rather than neurodegenerative, which sets it apart from the related CoA-pathway disorders PKAN (PANK2) and COPAN (COASY):

"In contrast to the neurodegenerative NBIA-related phenotypes associated with defects in PANK2 and COASY, PPCS-deficient individuals present with a clear dilated cardiomyopathy with a variable degree of severity and no neurodegeneration." (PMID:29754768)

Identifiers

Synonyms: PPCS deficiency disorder (PPCS DD); PPCS-related dilated cardiomyopathy; CMD2C; dilated cardiomyopathy 2C; phosphopantothenoylcysteine synthetase deficiency.

Data basis. All knowledge comes from aggregated case reports and series of individual patients. By 2025 the total was 12 patients from 7 families (PMID:40745475, Table 1). There is no registry or EHR-scale data.

2. Etiology

Primary cause. Biallelic germline PPCS variants. The variants are missense or in-frame changes, plus one intronic splice-region variant, that reduce PPCS protein stability and lower cellular CoA.

"Identified variants lead to reduced PPCS protein stability and decreased cellular CoA levels." (PMID:40745475)

No biallelic loss-of-function genotype has been seen. This suggests that complete PPCS loss is lethal:

"none of the new patients, similarly to previously reported cases, harbored biallelic loss of function variants, suggesting that this combination might be incompatible with life." (PMID:40745475)

Genetic risk factors. The only established ones are the causal PPCS alleles listed in §4. No GWAS, susceptibility locus, or modifier gene has been established. - In family F5, the proband also carried KCNH2 p.His1153Tyr (a VUS associated with LQT2). It did not segregate with QT prolongation, so it is not an established modifier.

Environmental and precipitating factors. These are hypotheses, not established causes. - Intercurrent infection or catabolic stress repeatedly precipitated decompensation: viral URTI (F1:II, three episodes), CMV infection (F2:II.1), and rhabdomyolysis during illness or poor feeding (F1:II, F4:II). - The authors suggest that the gut microbiome and dietary intake of CoA precursors (pantetheine) may modify expressivity. They note that some patients worsened after antibiotic-treated infections. This rests on fruit-fly data plus anecdote and is explicitly speculative:

"part of the variable expressivity of PPCS DD among patients and siblings sharing the same pathogenic variants could be explained by differences in microbiome profile and dietary intake of CoA precursors" (PMID:40745475)

• Serum pantothenate (vitamin B5) was normal in two affected siblings (74.95 and 73.84 µg/L; reference 37–147). Dietary B5 deficiency is therefore not the mechanism (PMID:29754768).

Protective factors. - No genetic protective factor is known. - Exogenous pantethine is the only candidate protective or therapeutic exposure. It bypasses the PPCS step (see §6 and §12).

Gene–environment interaction. The proposed interaction is CoA demand (fasting, infection, fatty-acid-dependent metabolism) acting on a reduced CoA biosynthetic capacity. This is inferred, not formally tested.

3. Phenotypes

The frequencies below are counted from the 12 patients in PMID:40745475 Table 1 (Iuso 2018 + Lok 2022 + 6 new cases). They are small-number estimates.

Key quotes: - Neuromuscular phenotype (PMID:35616428): "a female infant who presented in the neonatal period with hypotonia, a necrotizing myopathy with intermittent rhabdomyolysis and other extracardiac manifestations before developing a progressive and ultimately fatal dilated cardiomyopathy." - Severity and mortality (PMID:35616428): "Biallelic pathogenic variants in phosphopantothenoylcysteine synthetase, PPCS, are a rare cause of a severe early-onset dilated cardiomyopathy with high morbidity and mortality." - Variable expressivity within one sibship (PMID:29754768): "Four out of eight siblings exhibited dilated cardiomyopathy of varying severity, without apparent extracardiac manifestations."

Onset categories: HP:0003593 Infantile onset ✔ and HP:0011463 Childhood onset ✔ cover most cases. Juvenile and adult presentations also occur (14–21 y).

Quality of life. No formal QoL instrument has been used. Reported disability includes wheelchair-assisted ambulation (F1:II), limited exertional capacity, and transplant morbidity including a below-knee amputation after a TAH complication (F3:III.3).

4. Genetic and molecular information

Gene: PPCS (hgnc:25686; OMIM 609853; chr 1p34.2). The canonical isoform is NM_024664 (311 aa). A shorter isoform (NM_001077447, 138 aa) shares the C-terminus. Only the canonical 34-kDa protein was detected in fibroblasts (PMID:29754768). PPCS acts as a homodimer:

"in physiological conditions PPCS exists mainly as a dimer." (PMID:29754768)

Reported variants (NM_024664)

• Allele frequency: The two original missense variants were absent from gnomAD (12/2017) (PMID:29754768).
• Classification: ClinGen has not curated PPCS (no CGGV: record in cache). PanelApp Australia lists PPCS for DCM with biallelic inheritance. Per the repo rule, do not assign a validity tier yourself.
• Mechanism: loss of function (hypomorphic) through protein instability. It is not dominant negative. Parents are heterozygous carriers and asymptomatic.
• Somatic vs germline: germline only.
• Genotype–phenotype hypothesis (exploratory, n = 12):

"the p.Glu233Val variant leads to an isolated DCM presentation with variable expressivity" … "We hypothesize that the 'DCM only' phenotype arises when variants involve exon 3, while 'DCM plus' occurs when they involve exons 1 and 2" (PMID:40745475)

Exon 1 is proposed as a mutational hotspot.

Modifier genes, epigenetics, chromosomal abnormalities. - No modifier genes are established. - No epigenetic data exist. - There are no chromosomal causes. Incidental CNVs and runs of homozygosity were found, e.g. a 1p31.1 duplication in F2, which was considered unrelated.

5. Environmental information

• No toxin, occupational, or infectious etiology has been reported.
• Infections such as viral URTI and CMV act as decompensation triggers, not causes.
• One adult death (F6:IV.1, age 21) was from SARS-CoV-2 complications. Cardiac function in both siblings stayed stable through that infection (PMID:40745475).
• Lifestyle: avoiding fasting is plausible given the metabolic crises (hypoglycemia, rhabdomyolysis), but this is not evidence-based.

6. Mechanism and pathophysiology

Ordered causal chain

1. Biallelic hypomorphic PPCS variants, often missense in exon 1 or at the dimer interface or ATP site. These lead to reduced PPCS protein stability and abundance, with transcript levels normal in iPSC-derived cells.
2. Demonstrated in fibroblasts (PMID:29754768, 40745475) and in iPSCs, CPCs and cardiomyocytes. iPSC-CMs show "markedly reduced PPCS protein levels … suggesting impaired protein stability" with "no significant differences" in PPCS transcript (PMID:40745475).

3. Some variants also impair dimerization. In blue-native PAGE, no dimer was detectable in the Family A index (PMID:29754768).

4. Loss of PPCS enzyme activity, i.e. failure to condense 4'-phosphopantothenate with cysteine. This results in reduced de novo CoA biosynthesis.

5. The enzymatic step: "Phosphopantothenoylcysteine synthetase (PPCS) catalyzes the second step of the pathway during which phosphopantothenate reacts with ATP and cysteine to form phosphopantothenoylcysteine." (PMID:29754768)

6. Yeast complementation showed that the variants are deleterious.

7. Reduced intracellular CoA, which is rescued by re-expressing wild-type PPCS.

8. "Biochemical analysis revealed a decrease in CoA levels in fibroblasts of all affected individuals." (PMID:29754768)
9. The deficit grows as cells commit to the cardiac lineage (PMID:40745475): "The defect became significant and more pronounced during cardiac maturation to CPCs, d22 CMs, and d60 CMs in both lines".

10. Unlike PKAN and COPAN, PPCS deficiency lowers fibroblast CoA measurably.

11. (Inferred) Limited acyl-CoA formation, which leads to impaired long-chain fatty-acid activation and mitochondrial β-oxidation. Mature cardiomyocytes depend on fatty acids for energy, so this causes an energy shortfall.

12. Biochemical support: low long-chain acylcarnitines (2018) and a VLCADD-like acylcarnitine pattern during crises (2025).
13. Authors' reasoning (PMID:40745475): "iPSCs rely mainly on glycolysis for energy, while mature cardiac cells preferentially utilize fatty acids, requiring CoA for their activation and utilization. Therefore, a shortage of CoA during cardiac cell maturation could lead to reduced energy supply for cardiac cells and cause cardiac dysfunction"
14. 2018 mechanism (PMID:29754768): "Reduced cytosolic CoA concentration in PPCS-affected individuals may lead to a reduced synthesis of activated long-chain fatty acids … resulting in reduced long-chain acylcarnitine concentrations, similar to individuals with carnitine palmitoyltransferase I (CPT1) deficiency."

15. This step is inferred. CoA has not been measured in patient heart tissue, and fluxomics has not been done.

16. Cardiomyocyte structural and excitation–contraction defects. In iPSC-CMs these are:

17. sarcomere disorganization;
18. reduced Ca²⁺ transient amplitude;
19. arrhythmic events in 42–54% of cells.

In 3D engineered heart patches they are: - falling contractile force over time; - blunted force–frequency relationship; - shortened effective refractory period, i.e. a pro-arrhythmic substrate.

This is demonstrated in vitro (PMID:40745475): "Cardiac cells exhibit impaired contractility and arrhythmias, which are partially rescued by pantethine treatment."

1. Clinical consequences. The cellular defects lead to dilated cardiomyopathy with systolic failure, plus ventricular arrhythmia, VF arrest and sudden death. Episodes are often precipitated by infection or catabolism. Mild interstitial fibrosis and myocyte nucleomegaly were seen on endomyocardial biopsy (F1:II), with no myocarditis.

Branches

• Branch A, skeletal muscle (exon 1–2 genotypes). CoA deficit in skeletal muscle is associated with hypotonia, necrotizing myopathy, rhabdomyolysis during catabolic stress, and elevated CK. The mechanism is presumed to be the same energy and fatty-acid-oxidation failure, but this is not demonstrated.
• Branch B, systemic metabolic crisis. Hypoglycemia, lactic acidosis, hyperammonemia, and dicarboxylic aciduria during illness are consistent with secondary fatty-acid-oxidation and TCA impairment (inferred).
• Branch C, alternative or toxic-metabolite hypothesis. This is untested in humans:

"We cannot exclude that cardiomyopathy in PPCS-deficient individuals is also due to the generation of toxic metabolites. For instance, L-cysteine normally funneled in the synthesis of phosphopantothenoylcysteine could accumulate" (PMID:29754768)

Supporting evidence is limited to the report that dPPCS fly mutants are hypersensitive to cysteine.

Unexplained tissue selectivity.

"considering the ubiquitous presence of the enzymatic PPCS activity, it remains unexplained why the brain and in general the other organs are not affected" (PMID:29754768)

The 2025 paper suggests that tissue- or time-specific alternative isoforms may explain this. A transplant recipient (F3:III.3) has had no DCM recurrence at one year, which is consistent with a heart-intrinsic (cell-autonomous) defect.

Subcellular localization. PPCS shows nuclear and cytosolic signal in iPSC-derived cells and in GFP-tagged HeLa cells (PMID:40745475).

Suggested ontology terms

Molecular profiling. - Clinical RNA-seq of skeletal muscle in F1:II showed "an overall reduction in PPCS expression". - No GEO, proteomic, metabolomic, single-cell, or CRISPR-screen datasets are specific to this disease.

7. Anatomical structures affected

• Primary: heart (UBERON:0000948 ✔), mainly the left ventricle (UBERON:0002084 heart left ventricle ✔). Biventricular dysfunction occurred in F5 (RVEF 37%).
• Secondary:
• skeletal muscle (UBERON skeletal muscle tissue ⚠), in the exon 1–2 genotypes;
• liver, through transaminitis and coagulopathy (F4);
• pulmonary vasculature (PAH, 1 case);
• possibly the pituitary (suspected dysfunction, 1 case);
• the brain, with non-specific changes only and no iron accumulation.
• Cells: cardiomyocytes and skeletal myocytes. Fibroblasts are used for diagnosis.
• Subcellular: cytosol and nucleus (PPCS); mitochondria (downstream β-oxidation and acyl-CoA use).
• Laterality: not applicable (global ventricular dysfunction).

8. Temporal development

• Onset: ranges from antenatal and neonatal to 21 years.
• Severe compound-heterozygous or exon-1 cases present in the neonatal or infantile period.
• Glu233Val homozygotes span 23 months to 21 years.
• Pattern: acute decompensation on top of an insidious chronic course. Episodes are often triggered by infection.
• Progression: variable.
• Rapidly fatal in infancy in several cases: deaths at 3, 4 and 10 months, and at 23 months and 3 years.
• Others have chronic stable DCM into adulthood.
• Remission: some recovery of LV function occurred.
• F1:II improved spontaneously between episodes.
• F5:IV.1 had "fully recovered LV function" on pantethine plus standard heart-failure therapy.
• Critical period: the authors stress early treatment:

"complete reversal may require early intervention." (PMID:40745475)

9. Inheritance and population

• Inheritance: autosomal recessive (HP:0000007 ✔). Carriers are asymptomatic and segregation is complete in Family B/F6.
• Penetrance: appears complete for cardiomyopathy in homozygotes, with variable expressivity within sibships (mild vs fatal DCM among siblings with the same genotype).
• Anticipation and mosaicism: none reported.
• Consanguinity: 8 of 12 patients came from consanguineous families (Table 1).
• Founder effect: p.Glu233Val recurs in Family B/F6 (Arab-Muslim, Israel), F3 and F5. Haplotype analysis has not been reported, so a founder effect is plausible but unproven.
• Prevalence: unknown. There are 12 cases in the literature ("To date, only six patients worldwide have been identified" before the 2025 series). The appropriate dismech record would be measure_type: CASES_IN_LITERATURE, prevalence_class: ULTRA_RARE.
• Carrier frequency: not estimated. The 2018 in-house database of more than 11,000 exomes contained no other rare biallelic PPCS genotypes.
• Sex ratio: roughly balanced (both sexes affected).
• Geography and ancestry: German, Arab-Muslim (Israel), UK, North American, and other cohorts. The 2025 patients' ancestry is not fully given in the text read.

10. Diagnostics

Genetic testing (definitive). - Most cases were diagnosed by exome sequencing (singleton, trio, or reanalysis). One sibling was diagnosed by single-gene testing after cascade screening. Trio genome sequencing was used in Lok 2022. - PPCS is on PanelApp Australia's DCM panel. It may be missing from many commercial DCM panels, so exome or genome reanalysis was what found it in F1:II, years after a non-diagnostic exome. - CMA is not diagnostic. Mitochondrial DNA testing is useful to exclude mitochondrial differentials only.

Functional and biochemical tests (research-level). - Fibroblast PPCS immunoblot (reduced or absent 34-kDa band). - Fibroblast total CoA by fluorimetric kit (reduced; rescued by wild-type PPCS transduction). - Serum CoA and PPCS ELISA were undetectable in both patients and controls, so they are not useful (PMID:29754768).

Supportive laboratory findings. - Acylcarnitine profile: low C16/C18, or VLCADD-like C14:1/C14:2 elevation during crises. It can be normal when the patient is well, and its role as a biomarker is inconsistent. - CK, lactate, ammonia, glucose; urine organic acids (dicarboxylic aciduria); FGF21 was elevated in one case.

Cardiac work-up. - Echocardiography (LVEDD z-score, EF, FS) and cardiac MRI (volumes, LGE usually absent, LVNC ratio). - ECG (QT prolongation, T-wave inversion, low voltage) and Holter or implantable loop recorder. - Endomyocardial biopsy: no myocarditis; nucleomegaly and mild fibrosis; normal mitochondria on EM.

Differential diagnosis. - Other genetic DCMs (TTN, LMNA, sarcomeric). - Fatty-acid oxidation disorders: VLCADD (the acylcarnitines mimic it), CPT1 deficiency, primary carnitine deficiency. - Mitochondrial cardiomyopathies; Barth syndrome (males); Pompe disease (a GAA VUS was excluded in F2). - Viral myocarditis (cardiac MRI in F2 initially suggested it). - LQT syndromes (KCNH2). - Other CoA-pathway disorders, PKAN and COPAN, which are distinguished by NBIA on MRI.

Screening. No newborn screening exists. Acylcarnitine abnormalities are not consistent enough for NBS. Cascade testing of siblings is effective: F3:III.2 was diagnosed this way.

11. Outcome and prognosis

• Mortality: 7 of 12 have died.
• Deaths at 3 mo, 4 mo and 10 mo; at 23 mo and 3 y (DCM); and at 21 y (COVID-19).
• With one more early death in the series, the counts in Table 1 are hard to align exactly. Take the totals from Table 1 when curating.
• Causes were multi-organ failure, refractory arrhythmia, and cardiac arrest.
• Survivors: ages 11–21 y, with variable function. Outcomes include one heart transplant with no graft dysfunction at one year, one ICD carrier, and one person in a wheelchair.
• Prognostic factors (hypothesized):
• Genotype: exon 1–2 and compound-heterozygous genotypes are more severe; Glu233Val is "DCM only".
• Age at onset: neonatal or infantile onset is worse.
• Timing of pantethine start.
• No survival statistics or QoL measures exist.

12. Treatment

Targeted metabolic bypass: pantethine (compassionate use). Rationale (PMID:29754768):

"CoA biosynthesis can occur with pantethine as a source independent from PPCS, suggesting pantethine as targeted treatment for the affected individuals still alive."

Pantethine is cleaved to pantetheine, which PANK phosphorylates to 4'-phosphopantetheine, so the PPCS and PPCDC steps are skipped.

Dosing. - Family B: 6–8 mg/kg/day, titrated to 20–24 mg/kg/day. - F1:II: 450 mg/day (17 mg/kg/day), increased to 900 mg/day. - F5:IV.1: 600 mg/day (~10 mg/kg/day). - Family F6 long-term: ~15 mg/kg/day.

Clinical outcomes in the 4 treated patients. - Family B: "mild improvement in exertional dyspnea and an increase of ejection fraction … from 36% … to 48%" in IV.1; IV.4 stable at EF 45%. The 2018 authors were cautious: "Our results thus far had not shown significant clinical improvement." - F1:II: no further rhabdomyolysis; CK and BNP normalized; LV size normal with low-normal function. - F5:IV.1: fully recovered LV function, alongside ICD, beta-blocker and ACE inhibitor. - Summary (PMID:40745475): "Clinically, patients receiving pantethine show sustained improvement over time." - Evidence level: uncontrolled case reports confounded by standard heart-failure therapy.

In vitro evidence. - Pantethine at 50–500 µM raised CoA in fibroblasts, iPSCs, CPCs and CMs, without increasing PPCS protein. - It partially rescued sarcomere organization, Ca²⁺ transients and ERP. - It reduced arrhythmic events in CMs from 42% to 26% and from 54% to 24%. - 4'-phosphopantetheine raised fibroblast CoA less effectively than pantethine. - One unexplained observation: F1:II began excreting 3-methylcrotonylglycine after starting pantethine. He also carries a homozygous MCCC1 VUS.

Standard cardiac and supportive care. - Guideline-directed heart-failure therapy: beta-blockers (metoprolol), ACE inhibitors, milrinone and other inotropes, and carnitine supplementation (empirical, in F2). - ICD for secondary prevention after VF. - ECMO for acute decompensation. - Total artificial heart as a bridge, then heart transplantation, which was successful in F3:III.3. - For metabolic crises: dietary fatty-acid-oxidation management (initially treated as VLCADD), carglumic acid, and CVVH for hyperammonemia. - Rehabilitation and physical therapy for neuromuscular disability.

Experimental therapies. No registered trials were found for PPCS deficiency. 4'-phosphopantetheine has been tested in PKAN trials, but not in PPCS DD. No gene therapy or RNA therapy exists.

Pharmacogenomics: none.

Suggested NCIT terms (all are in the CLAUDE.md common list; still confirm with validate-terms):

13. Prevention

• Primary: none, beyond reproductive options.
• Secondary:
• Cascade genetic testing of siblings, with echocardiography, ECG and loop recorder for those found affected (F3:III.2 was found pre-symptomatically).
• Early pantethine start is proposed for genotype-positive individuals.
• Tertiary:
• Avoid prolonged fasting.
• Aggressive management of intercurrent infections.
• Arrhythmia surveillance and ICD where indicated.
• Vaccination (one COVID-19 death).
• Genetic counseling: AR with 25% recurrence risk for carrier couples; prenatal or preimplantation diagnosis is possible once familial variants are known. Consanguinity counseling is relevant.

14. Other species and natural disease

• No naturally occurring animal disease was found. A search of OMIA was not done, so treat this as unverified.
• Orthologs:
• S. cerevisiae CAB2/YIL083C (essential)
• D. melanogaster CG5629 (dPPCS)
• E. coli CoaBC (bifunctional PPCS/PPCDC)
• Zebrafish ortholog ZDB-GENE-060512-104 (from the ZFIN search result)
• Pathway conservation:

"The pathway of CoA de novo biosynthesis from vitamin B5 is conserved in eukaryotes and prokaryotes and consists of five consecutive enzymatic steps." (PMID:29754768)

15. Model organisms and systems

For dismech modeled_mechanisms: - The Drosophila model could link to the cardiac contractile/arrhythmia node with PARTIALLY_RECAPITULATES and SPECIES_MISMATCH + BOUNDARY_OMISSION divergences. - The iPSC-CM patch could link to the CoA deficiency node (RECAPITULATES, model_scale: CELLULAR) and to the DCM node. The DCM link is an upward extrapolation, so it needs limitations.

Gaps and open questions

1. CoA has never been measured in human or animal heart tissue. The fatty-acid-oxidation energy-deficit step is inferred.
2. It is unexplained why the heart is affected and the brain is not, given ubiquitous PPCS expression. The isoform hypothesis is unproven.
3. The genotype–phenotype rule (exon 3 vs exons 1–2) rests on n = 12.
4. Pantethine efficacy is uncontrolled, and the optimal dose and timing are unknown. 4'-phosphopantetheine has not been tested clinically.
5. The microbiome and dietary pantetheine contribution to expressivity has been shown only in flies.
6. There is no mammalian genetic model.
7. No ClinGen validity curation exists, and no Orphanet entry was verified.

Curation notes for the open Cardiomyopathy_Dilated_2C.yaml draft: - The draft currently has one stub node. It should be expanded along the six-step chain above. - Four PMIDs are now cached in references_cache/: 29754768, 35616428, 35397396, 40745475. 35616428 and 35397396 are abstract-only, so snippets from them must come from the abstract. - Before binding, look up the ⚠ terms: the PPCS molecular-function GO term, pantethine CHEBI, and skeletal muscle UBERON.

Sources

• PMC12313872 – Zhang et al. 2025, Commun Med (PMID:40745475)
• Springer Nature Communities – "Pantethine for a Rare Cardiomyopathy"
• University of Tübingen repository – Iuso et al. 2018 (PMID:29754768)
• PanelApp Australia – PPCS, Dilated Cardiomyopathy panel
• Cellosaurus MRIi028-A (CVCL_A0TH) and hPSCreg publication record (PMID:35397396)
• ZFIN ZDB-GENE-060512-104
• ERIBA – Sibon 2025 Commun Med

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Quotes not found in the cited source

Searched the abstract, any retrieved full text, and the title. A quote drawn from a part of the paper that was not retrieved will appear here too, so check before treating one as invented:

• PMID:40745475: "none of the new patients, similarly to previously reported cases, harbored biallelic loss of function variants, suggesting that this combination might be incompatible with life."
• closest text in source: "Genetically, none of the new patients, similarly to previously reported cases, harbored biallelic loss of fun ction variants, suggesting that this combination might be incompatible with life"

Term Validation

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

Every term resolved, and every label the report gave matched.