Confirming <scp><i>TBC1D32</i></scp>‐related ciliopathy in humans

Alsahan, Nada; Alkuraya, Fowzan S.

doi:10.1002/ajmg.a.61717

Cited by 9 publications

(4 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We now raise the number of reported pathogenic TBC1D32 variants, identified in 8 unrelated families, to 10: 1 missense (c.3513G>T), 2 nonsense (c.1267G>T; c.3724C>T), 3 splicing (c.317+5G>A; c.1141-1G>A; c.1372+1G>T), and 4 indels (c.18_27del; c.846delTCCT; c.1165_1166dup; c.2151del) (refs. 32 – 34 and this study). Although it is possible that nonsense and indel TBC1D32 variants result in loss of function, splicing and missense variants are more ambiguous.…”

Section: Discussionsupporting

confidence: 62%

“…Clinical symptoms ranged from midline cleft, anophthalmia, polydactyly to choanal atresia, agenesis of corpus callosum, vermis and pituitary hypoplasia, and hydrocephalus. Subsequently, 7 patients from 5 families were reported as carrying different pathogenic TBC1D32 variants and presenting with syndromic ciliopathies ( 32 ). It is noteworthy that 1 patient from a Finnish family with compound heterozygous indels in TBC1D32 also exhibited a progressive retinal dystrophy, but this was not further explored ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa

Bocquet,

Borday,

Erkilic

et al. 2023

JCI Insight

View full text Add to dashboard Cite

Retinitis pigmentosa (RP) is the most common inherited retinal disease (IRD) and is characterized by photoreceptor degeneration and progressive vision loss. We report 4 patients presenting with RP from 3 unrelated families with variants in TBC1D32 , which to date has never been associated with an IRD. To validate TBC1D32 as a putative RP causative gene, we combined Xenopus in vivo approaches and human induced pluripotent stem cell–derived (iPSC-derived) retinal models. Our data showed that TBC1D32 was expressed during retinal development and that it played an important role in retinal pigment epithelium (RPE) differentiation. Furthermore, we identified a role for TBC1D32 in ciliogenesis of the RPE. We demonstrated elongated ciliary defects that resulted in disrupted apical tight junctions, loss of functionality (delayed retinoid cycling and altered secretion balance), and the onset of an epithelial-mesenchymal transition–like phenotype. Last, our results suggested photoreceptor differentiation defects, including connecting cilium anomalies, that resulted in impaired trafficking to the outer segment in cones and rods in TBC1D32 iPSC-derived retinal organoids. Overall, our data highlight a critical role for TBC1D32 in the retina and demonstrate that TBC1D32 mutations lead to RP. We thus identify TBC1D32 as an IRD-causative gene.

show abstract

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa

Bocquet,

Borday,

Erkilic

et al. 2023

JCI Insight

View full text Add to dashboard Cite

show abstract

“…, 2017 ; Shaheen et al. , 2019 ; Alsahan and Alkuraya, 2020 ; Hietamäki et al. , 2020 ; Siegert et al.…”

Section: Discussionmentioning

confidence: 99%

BROMI/TBC1D32 together with CCRK/CDK20 and FAM149B1/JBTS36 contributes to intraflagellar transport turnaround involving ICK/CILK1

Satoda

Noguchi

Fujii

et al. 2022

MBoC

View full text Add to dashboard Cite

show abstract

“…To date, variants in TBC1D32 have been reported in seven individuals (Adly et al, 2014; Alsahan & Alkuraya, 2020; Hietamäki et al, 2020; Monies et al, 2019); however, TBC1D32 has no associated phenotype cataloged in Online Mendelian Inheritance in Man (OMIM). We present seven additional probands, including four with severe prenatal phenotypes, associated with TBC1D32 gene variants to provide additional data on the spectrum of phenotypes associated with this complex ciliopathy.…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of TBC1D32‐associated conditions: Expanding the phenotypic spectrum of a complex ciliopathy

Harris

Chitayat

Gilmore

et al. 2023

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development. We describe seven unpublished probands with rare likely pathogenic variants or variants of uncertain significance that segregate with recessive disease in TBC1D32, including four fetal probands in three unrelated pedigrees and three pediatric probands in unrelated pedigrees. We also report clinical comparisons with seven previously published patients. Index probands were identified through an ongoing prenatal exome sequencing study and through an online data sharing platform (Gene Matcher™). A literature review was also completed. TBC1D32 is involved in the development and function of cilia and is expressed in the developing hypothalamus and pituitary gland. We provide additional data to expand the phenotype correlated with TBC1D32 variants, including a severe prenatal phenotype associated with life‐limiting congenital anomalies.

show abstract

Confirming TBC1D32‐related ciliopathy in humans

Cited by 9 publications

References 5 publications

TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa

TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa

BROMI/TBC1D32 together with CCRK/CDK20 and FAM149B1/JBTS36 contributes to intraflagellar transport turnaround involving ICK/CILK1

Diagnosis of TBC1D32‐associated conditions: Expanding the phenotypic spectrum of a complex ciliopathy

Contact Info

Product

Resources

About