Skip to main page content (V体育安卓版)
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. VSports app下载.

Https

The site is secure V体育官网. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. .

Review
. 2023 May;191(5):1282-1292.
doi: 10.1002/ajmg.a.63150. Epub 2023 Feb 24.

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

Sarah C Harris  1 , Karen Chong  2 , David Chitayat  2 , Kelly L Gilmore  3 , Alexander A L Jorge  4 , Bruna L Freire  5 , Antonio Lerario  6 , Patrick Shannon  7 , Heidi Cope  8 , William B Gallentine  9 , Gwenal Le Guyader  10 , Frederic Bilan  10   11 , Pascaline Létard  10 , Erica E Davis  12   13   14 , Neeta L Vora  3
Affiliations
Review

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

Sarah C Harris et al. Am J Med Genet A. 2023 May.

"V体育安卓版" Abstract

Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development VSports手机版. We describe seven unpublished probands with rare likely pathogenic variants or variants of uncertain significance that segregate with recessive disease in TBC1D32, including four fetal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. .

Keywords: TBC1D32; ciliopathy; exome sequencing; prenatal phenotype V体育安卓版. .

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
TBC1D32 Schematic. (a) Genomic locus on chr6:121,079,494–121,334,480 (GRCh38, reverse strand). Blue boxes, exons; white boxes, untranslated regions; dashed lines, introns; exons harboring case-associated variants are labeled at the bottom. (b) Location of variants on a linear protein schematic; amino acids are labeled at the bottom. For both panels: teal asterisks, hitherto unreported case-associated variants; magenta asterisks, previously published pathogenic variants.
FIGURE 2
FIGURE 2
Pedigrees of previously unpublished TBC1D32 variants that segregate with disease (variants are heterozygous unless indicated otherwise in each pedigree).
FIGURE 3
FIGURE 3
Facies comparison of similar facies of Proband 3 (a) and Proband 4 (b). Proband 3 (a) with an enlarged head with microphthalmia and hypotelorism. The columella is absent, resulting in a fused single nostril although the nasal septum is present internally. The philtrum is long with a wedge-shaped depression below the fused nostril, and there is micrognathia. Comparison of hands of Proband 3 (C) and Proband 4 (D). Proband 4 (D) with hypoplastic, poorly demarcated middle phalanges on digits 2–5, with short, thick fingers.
FIGURE 4
FIGURE 4
Central nervous system. The inferior surface of the brain in Proband 3 (a) and Proband 4 (b) demonstrates well-marked interhemispheric fissure with absent olfactory bulbs and tracts, absent infundibulum, and single, thick fused optic nerve (arrow). Section through optic nerve in Proband 3 (c) and Proband 4 (d) demonstrating rosettes of ciliated neuroepithelial elements resembling fetal retina. Coronal sections in Proband 3 (e) and Proband 4 (f) demonstrate small fused thalamus (arrow) with massive ventriculomegaly and thinning of the cortical mantle. In both cases, the midbrain was small and the aqueduct stenotic: Cross sections of the cerebellum and pons in Proband 3 (g) and Proband 4 (h) demonstrate a minute fourth ventricle, a poorly demarcated cerebellar vermis, and absent corticospinal tracts.
FIGURE 5
FIGURE 5
Internal structures. Comparison of skull bases of Proband 3 (a) and Proband 4 (b). Proband 3 (a) with absent sella turcica. Arrow indicates fused optic nerve. No pituitary was present, even on subserial sectioning of the sphenoid. Proband 4 (b) demonstrates wide, shallow sella anterior to (arrow) fused optic nerve. A small pituitary was present. In both fetuses, the hypothalamus was disorganized and no infundibulum was present. Retroperitoneum demonstrating small adrenal glands (arrows) in Proband 3 (c) and Proband 4 (d).
See this image and copyright information in PMC

References

    1. Adly N, Alhashem A, Ammari A, & Alkuraya FS (2014). Ciliary genes TBC1D32/C6orf170 and SCLT1 are mutated in patients with OFD type IX. Human Mutation, 35(1), 36–40. 10.1002/humu.22477 - V体育平台登录 - DOI - PubMed
    1. Alsahan N, & Alkuraya FS (2020). Confirming TBC1D32-related ciliopathy in humans. American Journal of Medical Genetics. Part A, 182(8), 1985–1987. 10.1002/ajmg.a.61717 - DOI - PubMed
    1. Bruel AL, Franco B, Duffourd Y, Thevenon J, Jego L, Lopez E, Deleuze JF, Doummar D, Giles RH, Johnson CA, Huynen MA, Chevrier V, Burglen L, Morleo M, Desguerres I, Pierquin G, Doray B, Gilbert-Dussardier B, Reversade B, … Thauvin-Robinet C (2017). Fifteen years of research on oral-facial-digital syndromes: From 1 to 16 causal genes. Journal of Medical Genetics, 54(6), 371–380. 10.1136/jmedgenet-2016-104436 - DOI - PMC - PubMed
    1. Gray KJ, Wilkins-Haug LE, Herrig NJ, & Vora NL (2019). Fetal phenotypes emerge as genetic technologies become robust. Prenatal Diagnostica, 39(9), 811–817. 10.1002/pd.5532 - DOI - PMC - PubMed
    1. Gurrieri F, Franco B, Toriello H, & Neri G (2007). Oral-facial-digital syndromes: Review and diagnostic guidelines. American Journal of Medical Genetics. Part A, 143A(24), 3314–3323. 10.1002/ajmg.a.32032 - DOI - PubMed

Substances