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Genetic analysis of an Iranian patient with Pseudo-TORCH syndrome

Masoumeh RostamiComperhencive Center for Genetic Services(CCGS)

Shahid Beheshti Uni. Of med. Sci.

Index

Clinical Presentation

Genetic workup

OCLN Gene

Pseudo-TORCH syndrome-1

TORCH Syndrome

Comparison

Clinical Presentation

A 37 day-old infant boy result of C/S with clinical diagnosis ofmicrocephaly at birth, intractable seizure, respiratory distress andinsufficiency, abnormal CT scan(calcification in brain, basal ganglia,thalamus), choroid plexus cyst.

The parents are first cousins

History of hypothyroidisms, two abortions (FHR-) in mother andmicrocephaly in the family.

Pedigree

Torch syndrome: Yes or No

Diagnosis of primary familial cranial calcification and TORCHsyndrome.

Metabolic tests: Negative

TORCH tests : Negative

What should be done???

Genetic workup

Genetic counseling

Whole Exome Sequencing (WES):analyzed using various bioinformatics databases and software including PolyPhen, SIFT, Mutation Taster and CADD.

Confirmation of WES results with Sanger.

WES Results

OMIM

ACMG Classification

Sequencing Results

OCLN Gene

OCLN gene:On chromosome 5q13, 9 Exons , Protein Coding gene.

Encodes an integral membrane protein (Occludin) that is required for formation and regulation of the tight junction Paracellular permeability barrier.

Mutation in OCLN :Caused band-like calcification with simplified gyration and polymicrogyria (BLC-PMG) → Pseudo-Torch Syndrome 1

Diseases associated with OCLN include Pseudo-Torch Syndrome 1 and Torch Syndrome. Among its related pathways are Development Slit-Robo signaling and Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 Signaling Pathways.

Identified a homozygous 22-bp deletion (173_194del22) in exon 3 of the OCLN gene, resulting in a frameshift and deletion of the first 10 amino acids of the conserved Marvel domain.

Occludin Protein

Pseudo-Torch Syndrome-1

Pseudo-TORCH syndrome-1: An autosomal recessive neurologic disorder withcharacteristic clinical and neuroradiologic features that mimic intrauterine TORCHinfection in the absence of evidence of infection.

Extremely rare inherited with the incidence of 1/1,000,000.

Symptomes: Congenital microcephaly, intracranial calcifications, severdevelopmental delay, simplified gyration, polymicrogyria and Seizure.

Caused by homozygous or compound heterozygous mutation in the OCLN gene

TORCH Syndrome

TORCH Syndrome refers to infection of a developing fetus or newborn by a groupof infectious agents.

TORCH Syndrome results from one of the TORCH agents having crossed theplacenta during pregnancy

(T)oxoplasmosis, (O)ther Agents, (R)ubella (also known as German Measles), (C)ytomegalovirus and (H)erpes Simplex.

Symptomes : Periventricular calcifications, Microcephaly, seizures and Hydrocephalus.

Comparison