Congenital anomalies of the kidney and urinary tract (CAKUT) Syndromic

Gene: KIF14

Green List (high evidence)

At least 8 families reported with a primary microcephaly disorder. Microcephaly ranged from -3.6 to -11 SD. One family reported with a Meckel phenotype presenting antenatally, separate gene-disease association not established. Note that CAKUT-type abnormalities have been described in the families with primary microcephaly and so this may represent the severe end of the spectrum for this condition rather than a separate disease entity.

Created: 1 Sep 2020, 5:41 a.m. | Last Modified: 1 Sep 2020, 5:41 a.m.

Panel Version: 0.4085

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly 20, primary, autosomal recessive, MIM# 617914; Meckel syndrome 12, MIM# 616258

Publications

• 28892560
• 29343805
• 24128419

Green List (high evidence)

1 family with 2 sib fetuses with features consistent with Meckel syndrome, with KIF14 mutations which segregated with the disorder in the family


Mutations in KIF14 have previously been associated with either severe, isolated or syndromic microcephaly with renal hypodysplasia (RHD). Four families with fetuses presenting with the syndromic form and harbouring biallelic variants in KIF14. The functional analyses showed that the identified variants severely impact the activity of KIF14 and likely correspond to loss-of-function mutations. In vitro and in vivo analyses did not provide evidence of a direct role for KIF14 in ciliogenesis and suggested that loss of kif14 causes ciliopathy-like phenotypes through an accumulation of mitotic cells in ciliated tissues. Altogether, the results demonstrate that KIF14 mutations result in a severe syndrome associating microcephaly and RHD through its conserved function in cytokinesis during kidney and brain development.
Sources: Literature

Created: 3 Jan 2020, 4:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microcephaly 20, primary, autosomal recessive, OMIM #617914; ?Meckel syndrome 12, OMIM #616258

Publications

• PMID: 30388224. 24128419