Proteinuric renal disease

Gene: TBC1D8B

Comment on phenotypes: Previously:
Steroid-resistant nephrotic syndrome

Created: 8 Jul 2021, 10:41 a.m. | Last Modified: 8 Jul 2021, 10:41 a.m.

Panel Version: 2.51

Green List (high evidence)

Comment on mode of inheritance: PMID: 30661770 - 2 carrier (heterozygous) females in family A developed proteinuria at age 7 and as an adult (later than males).

Created: 1 Apr 2019, 9:15 p.m.

Comment on list classification: 2 unrelated families plus functional evidence

Created: 1 Apr 2019, 9:10 p.m.

Not listed in OMIM or Gene2Phenotype

PMID: 30661770 - Dorval et al 2019 - by exome sequencing, they identified missense mutations (c.738G>C and c.872T>C) in TBC1D8B in two families with an X-linked early-onset SRNS with FSGS. Immunofluorescence studies revealed TBC1D8B presence in human glomeruli, and affected individual podocytes displayed architectural changes associated with migration defects commonly found in FSGS. In zebrafish they demonstrated that both knockdown and knockout of the unique TBC1D8B ortholog-induced proteinuria and that this phenotype was rescued by human TBC1D8B mRNA injection, but not by either of the two mutated mRNAs. They also showed an interaction between TBC1D8B and Rab11b, a key protein in vesicular recycling in cells.

Family A (Ecuador) - affected females (I-2 and II-2) exhibited non-nephrotic proteinuria, while affected boys (II-1, II-3, and II-4) developed congenital or early-onset NS. Family B (UK) - sporadic SRNS-affected individual (II-2) in family B. The affected individual (II-2), a male from European ancestry presenting with early-onset SRNS at the age of 2 years, had no other systemic features. Both mutations segregated with the affected status in the respective families and were, respectively, present in 1/27,314 (with no hemizygous) and absent from gnomAD database in the population-matched control subjects.

Created: 1 Apr 2019, 9:09 p.m.

This gene was part of an initial gene list collated by Elizabeth Watson, North Bristol NHS Trust, February 2019 on behalf of the GMS Renal Specialist Test Group. Gene Symbol submitted: TBC1D8B; Suggested initial gene rating: green; Evidence for inclusion: PMID: 30661770 ; Other comments: Two unrelated families with rare variants, plus supporting functional evidence

Created: 4 Feb 2019, 10:41 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Publications

• PMID: 30661770