CAKUT

Gene: EXOC3L2

Comment on list classification: Agreed by Helen Brittain (Genomics England clinical team) that Amber rating is appropriate here: only one case that didn't lead to fetal demise. Added 'watchlist' tag awaiting further cases.

Created: 18 May 2020, 8:15 a.m. | Last Modified: 18 May 2020, 8:15 a.m.

Panel Version: 1.111

Comment on list classification: Gene was added to panel and rated Green by Chirag Patel. Updated rating from Grey to Amber. Most reported cases are from fetuses (e.g. PMID: 27894351) and therefore EXOC3L2 is more appropriate on Fetal panel.

Created: 30 Apr 2020, 4:46 p.m. | Last Modified: 30 Apr 2020, 4:46 p.m.

Panel Version: 1.75

PMID: 27894351: Shaheen et al., 2016 examined 371 individuals from 265 families with ciliopathy phenotypes. They identified a LOF variant in EXOC3L2 and a lethal phenotype that resembles Meckel–Gruber syndrome (severe posterior fossa malformation with kidney enlargement) in one family.

Created: 30 Apr 2020, 4:45 p.m. | Last Modified: 30 Apr 2020, 4:45 p.m.

Panel Version: 1.74

PMID: 28749478: Shamseldin et al., 2018 performed exome sequencing as part of molecular autopsy in a cohort of 44 families with at least one death or lethal fetal malformation. They report one fetus with a biallelic EXOC3L2 variant and a phenotype similar to Meckel-Gruber syndrome.

Created: 30 Apr 2020, 4:45 p.m. | Last Modified: 30 Apr 2020, 4:45 p.m.

Panel Version: 1.74

PMID:30327448: Shalata et al., 2019 report 4 patients (2 unrelated families) with homozygous variants in EXOC3L2. In the first family, a missense p.Leu41Gln variant was found in 3 fetuses. All had severe forms of Dandy-Walker that were detectable by prenatal ultrasound. Examination of kidneys was unremarkable. In the second family, the affected child carried a nonsense p.Arg72* variant. He had severe renal dysplasia amongst his phenotypes.

Created: 30 Apr 2020, 4:27 p.m. | Last Modified: 30 Apr 2020, 4:27 p.m.

Panel Version: 1.74

Green List (high evidence)

Four individuals from two unrelated families with brain, kidney and bone marrow abnormalities; another described as part of fetal autopsy series, and another in a ciliopathy cohort.
Sources: Literature

Created: 16 Jan 2020, 3:46 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dandy-Walker malformation; renal dysplasia; bone marrow failure

Publications

• PMID: 30327448, 28749478, 27894351