Status: I've read the existing entry and its cached sources, and found OMIM 618415. Running one more search for other DNMBP cataract reports, then I'll write the report.

Cataract 48 (CTRCT48; DNMBP-related autosomal recessive infantile cataract): research report

Scope. Only two publications report human DNMBP cataract: the 2018 gene-discovery paper (PMID:30290152) and one 2023 Turkish exome cohort (PMID:37592116). Web searches for 2024–2026 reports, including Chinese, Indian and Saudi pediatric cataract cohorts, found nothing new. The PubMed search tool was not authorized this session, so I checked abstracts against the local references_cache/ files and web search. A PubMed search filtered to 2024 onward would be the next step to confirm nothing newer exists.

Quotes below are copied from the cached abstracts or full text.

1. Disease information

• Definition. A non-syndromic, autosomal recessive cataract with bilateral lens opacity starting in infancy. It is caused by biallelic loss-of-function variants in DNMBP on chromosome 10q24. OMIM-derived records describe it as "characterized by infantile or early-childhood cataracts and visual impairment" (MGI disease page, OMIM:618415).
• Identifiers.
• MONDO:0032735 (cataract 48)
• OMIM 618415
• Gene: DNMBP, hgnc:30373
• Orphanet: no DNMBP-specific record found. It falls under Orphanet's general early-onset non-syndromic cataract grouping.
• ICD-10: Q12.0 (congenital cataract)
• MeSH: Cataract / Cataract, congenital
• Synonyms. CTRCT48; DNMBP-related cataract; autosomal recessive infantile cataract, DNMBP-related.
• Data source. Everything known comes from individual families: 12 affected people in 3 Pakistani families, plus 1 Turkish proband. There is no registry or EHR data.

2. Etiology

• Cause. Homozygous truncating DNMBP variants. "We therefore conclude that DNMBP loss-of-function variants cause infantile-onset cataracts in humans" (PMID:30290152).
• Genetic risk factor. Consanguinity. Every confirmed homozygous family was consanguineous; the Turkish Family 6 proband was the child of a first-cousin marriage.
• Environmental, protective and gene–environment factors. None reported. Not applicable to a fully penetrant Mendelian lens defect as far as the literature shows.

3. Phenotypes

• Gaps.
• The Pakistani abstract does not state the cataract morphology.
• No reports of nystagmus, amblyopia or aphakic glaucoma, and no extra-ocular features. The disease is reported as non-syndromic.
• Quality of life. No disease-specific data. The general burden is that of infantile cataract: risk of deprivation amblyopia and lifelong optical correction after surgery.

4. Genetics and molecular information

Gene. DNMBP encodes Tuba (dynamin-binding protein). It is a multi-SH3 scaffold with a central Dbl homology (DH) domain and a BAR domain (PMID:14506234).

Reported alleles. All are homozygous unless noted.

• Variant origin. Germline. Parents were heterozygous carriers.
• Functional consequence. Loss of function. The truncations remove the DH (Cdc42 GEF) domain and the C-terminal domains.
• Not reported. Modifier genes, epigenetic findings, chromosomal abnormalities and population allele frequencies for these specific variants (check gnomAD per variant).
• ClinGen. No gene-disease validity classification was found in the local cache.

5. Environmental information

Not applicable. No environmental, lifestyle or infectious contribution has been reported.

6. Mechanism and pathophysiology

Causal chain. Steps 4 and 5 are inferred, not shown in a lens.

1. Biallelic truncating DNMBP variants lead to loss of Tuba protein, or of its DH domain at least. Inferred from variant class; no patient protein studies.
2. Loss of Tuba removes a Cdc42-specific guanine nucleotide exchange factor.
3. "A Dbl homology domain present in the middle of Tuba … activates Cdc42, but not Rac and Rho" (PMID:14506234, in vitro).
4. Reduced local Cdc42 / N-WASP activity at the apical junction results in disordered junctional F-actin and E-cadherin assembly, with "curved and slack" junctions.
5. "At the subcellular level, Tuba inactivation modified the assembly pattern of junctional F-actin and E-cadherin."
6. "Suppression of Cdc42 activity or depletion of N-WASP … mimicked the effects of Tuba depletion."
7. Source: PMID:17015620, cultured non-lens epithelial cells.
8. In the eye, junction disorganization affects the cells that build the lens.
9. Fly evidence: knockdown of the ortholog sif "affects the development of these cells as well as the localization of E-cadherin, alters the distribution of septate junctions in adjacent cone cells," and cuts ERG amplitude by about 50% (PMID:30290152, Drosophila).
10. Extrapolation to vertebrate lens epithelium is untested.
11. Disrupted E-cadherin-dependent lens development is proposed to cause loss of lens transparency.
12. "E-cadherin has an important role in lens vesicle separation and lens epithelial cell survival in humans" (PMID:30290152).
13. This is the authors' background rationale, not an experimental result.
14. Loss of lens transparency produces bilateral infantile, sometimes lamellar, cataract and visual impairment.

Ontology suggestions.

Profiling. There are no transcriptomic, proteomic, metabolomic or single-cell studies of DNMBP cataract.

7. Anatomy

There is no secondary organ involvement.

8. Temporal development

• Onset. Infantile. The Turkish proband was diagnosed at 5 months and had surgery at 11 months.
• Progression. Natural history is not described. As with other developmental cataracts, the opacity is presumed to be stable or slowly progressive.
• Critical period. The amblyopia window in the first months of life is when surgery and optical rehabilitation matter most. This is general infantile-cataract knowledge, not DNMBP-specific.

9. Inheritance and population

• Inheritance. Autosomal recessive (HP:0000007), with complete penetrance in the families reported.
• Prevalence. Unknown. There are 4 confirmed families: 3 Pakistani and 1 Turkish.
• Founder effect, carrier frequency and sex ratio. Not reported. Sexes are not separately described in the abstract.
• Population pattern. Concentrated in consanguineous populations.

10. Diagnostics

• Clinical exam. Slit-lamp examination and red-reflex testing. CTRCT48 cannot be clinically distinguished from other infantile cataracts.
• Genetic testing. Exome sequencing or a congenital-cataract gene panel. Confirm DNMBP is included, since it is a rarely tested gene. Follow with segregation analysis.
• Suggested NCIT term: NCIT:C101295 Whole Exome Sequencing.
• In the Turkish cohort, exome sequencing found a pathogenic or likely pathogenic variant in 7 of 12 families (58%) (PMID:37592116).
• Biomarkers. None.
• Differential diagnosis. Other autosomal recessive infantile cataracts (e.g., LSS, FYCO1, CRYBB1, GCNT2); dominant crystallin and connexin cataracts; and syndromic or metabolic cataracts, such as galactosemia, which should be excluded biochemically.

11. Outcome and prognosis

• Life expectancy is expected to be normal. There are no systemic features.
• Visual outcome depends on timely surgery and amblyopia management. No DNMBP-specific outcome data exist.

12. Treatment

• Surgery. Lensectomy or cataract extraction (NCIT:C157809 Cataract Surgery), followed by aphakic or IOL optical correction. Both Turkish DNMBP probands had surgery at 11 months.
• Rehabilitation. Amblyopia therapy, such as occlusion.
• Other therapies. There is no pharmacological, gene-targeted or other DNMBP-specific therapy, and no clinical trials.

13. Prevention

• Genetic counseling for consanguineous families, with a 25% recurrence risk for parents who are both carriers.
• Carrier testing and prenatal or preimplantation testing are possible once the familial variant is known.
• Early detection through newborn red-reflex screening.

14. Other species

• No naturally occurring DNMBP cataract is recorded in OMIA from this search.
• Drosophila ortholog: still life (sif).

15. Model organisms

• Drosophila sif RNAi (PMID:30290152). Knockdown disrupts development of the lens-secreting cells, E-cadherin localization and septate-junction distribution, and roughly halves ERG amplitude in young flies.
• Limitation: the insect corneal lens is a secreted cuticular structure, not a crystallin-filled cellular lens. The model shows a junctional defect, not opacity.
• Vertebrate models. No vertebrate (mouse or zebrafish) lens model of DNMBP loss has been described. This is the main gap in the evidence for the mechanism.
• In vitro. Tuba knockdown in simple epithelial cell lines (PMID:17015620) is the main mechanistic system.

Key evidence gaps

1. Only 4 confirmed families have been reported.
2. Cataract morphology in the Pakistani families is not in the abstract.
3. No vertebrate lens model exists.
4. There is no ClinGen classification.
5. Whether the Turkish compound-heterozygous missense variants are pathogenic is unresolved.

Note on the existing knowledge base entry

kb/disorders/Cataract_48.yaml already covers this material: the same 4 alleles, the causal chain marked as inferred, Drosophila model caveats, and surgery evidence. This report found no new primary literature that would change the entry.

Sources - PMID:30290152, Ansar et al., Am J Hum Genet 2018, doi:10.1016/j.ajhg.2018.09.004; PMC6174361 - PMID:37592116, Türkyılmaz et al., Int Ophthalmol 2023, doi:10.1007/s10792-023-02857-1 - PMID:14506234 (Tuba, Cdc42-specific DH domain); PMID:17015620 (Tuba regulates junction configuration) - MGI disease page, OMIM:618415 - FlyBase FBrf0240231 - Texas Children's news release - KTU AVESIS record of the Turkish study - GeneBe DNMBP - Houston Methodist scholars page - EyeSmart, Medical Dialogues, CRST Europe, NZ Optics

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:

Every one of these was searched against an abstract alone, with no full text retrieved - marked abstract only below. Where full text can be fetched, re-running with it will settle them; where the source publishes only a summary to PubMed, as GeneReviews chapters do, it will not, and the quote has to be checked by hand against the chapter itself.

• PMID:14506234 (abstract only): "A Dbl homology domain present in the middle of Tuba … activates Cdc42, but not Rac and Rho"
• closest text in source: "A Dbl homology domain present in the middle of Tuba upstream of a Bin/amphiphysin/Rvs (BAR) domain activates Cdc42, but not Rac and Rho, and may thus cooperate with the C terminus of the protein in regulating actin assembly"

References that may not be about this subject

These identifiers resolve, so they are not fabrications, but the records they resolve to share almost none of this report's vocabulary. That is a clue and not a verdict - a paper can be relevant in ways its title and abstract do not spell out - so read them before deciding:

• PMID:14506234 (3 mentions) - Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology domains, links dynamin to regulation of the actin cytoskeleton.
• shared terms: tuba

Weighed against this report's own most characteristic terms: cataract, dnmbp, turkish, variant, lens, infantile, found, familie, pakistani, surgery, proband, tuba, affected, bilateral, gene, abstract, amblyopia, autosomal, recessive, visual.

Term Validation

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

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: OMIM.

17 of 18 terms resolved to a current term; the rest could not be looked up either way.