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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
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