Nephrocalcinosis or nephrolithiasis

Gene: STRADA

Red List (low evidence)

Seems to be associated with polyhydramnios

Created: 30 Oct 2019, 11:59 a.m. | Last Modified: 30 Oct 2019, 11:59 a.m.

Panel Version: 1.23

Despite red rating from reviewer, there is some published evidence that nephrocalcinosis is reported in patients with Polyhydramnios, so keeping green rating for now.

Created: 30 Oct 2019, 1 p.m. | Last Modified: 30 Oct 2019, 1 p.m.

Panel Version: 1.23

Associated with Polyhydramnios, megalencephaly, and symptomatic epilepsy #611087 (AR) in OMIM with nephrocalcinosis listed in the clinical features (for some patients).

PMID: 30311510 - Nelson et al 2018 - 2 sisters from nonconsanguineous parents with STRADA gene deletion of exons 7-9. Phenotypic characteristics of both with seizures. Both also had nephrocalcinosis and one sister also had nephrolithiasis.

PMID: 28688840 - Evers et al 2017 - in girl of 16 years from consanguineous Turkish parents they report a homozygous frameshift variant (c.891dupC / p.(C298Lfs*11) in STRADA was found from exome sequencing to cause a severe NDD with early onset epilepsy, brain anomalies, hypotonia, heart defect, nephrocalcinosis, macrocephaly and distinctive facies so far designated as PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome.

PMID: 27170158 - Bi et al 2016 - 4-year-old Indian male with global developmental delay, history of failure to thrive, infantile spasms, repetitive behaviors, hypotonia, low muscle mass, marked joint laxity, and dysmorphic facial features including tall forehead, long face, arched eyebrows, small chin, wide mouth, and tented upper lip. A homozygous single nucleotide duplication, c.842dupA (p.D281fs), in exon 10 of STRADA was identified. A renal ultrasound at 4 years 7 months showed medullary nephrocalcinosis, bilateral pelviectasis, and normal renal morphology and size.

PMID: 17522105 - Puffenberger et al 2007 - used single nucleotide polymorphism (SNP) microarrays to investigate the cause of a symptomatic epilepsy syndrome in a group of seven distantly related Old Order Mennonite children. They shared a homozygous deletion encompassing exons 9–13 of LYK5 (now known as STRADA). Nephrocalcinosis was found by renal ultrasound in 2 patients (only 4 had renal ultasounds)

>3 cases with nephrocalcinosis reported so keep green rating.

Created: 20 Oct 2019, 10:35 p.m. | Last Modified: 20 Oct 2019, 10:35 p.m.

Panel Version: 1.20

Green List (high evidence)

added gene after ID panel review, suggested by clinical team to add this gene to this panel

Created: 16 Jul 2018, 10:20 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polyhydramnios, megalencephaly, and symptomatic epilepsy, 611087

Publications

• 27170158
• 17522105
• 28688840