GM27158

GM27158 LCL from B-Lymphocyte

Description:

CEREBRAL ARTERIOPATHY, AUTOSOMAL DOMINANT, WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY, TYPE 1; CADASIL1
NOTCH, DROSOPHILA, HOMOLOG OF, 3; NOTCH3

Affected:

Yes

Sex:

Female

Age:

38 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
PIGI Consented Sample

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Ethnicity

Not Hispanic/Latino

Ethnicity

Irish, English, German

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; onset of symptoms at 31 years of age; diagnosed by a neurologist at 35 years; no visible abnormalities; supraclavicular lymphadenopathy; transient ischemic attack; bradycardia; vasovagal syncope; fatigue; lead exposure; recurrent urinary tract infection; blurred vision; decreased memory; cold intolerance; excessive thirst; anti-TPO antibodies; MRI revealed sinus arrhythmia, sinus bradycardia, sinus rhythm and sinus tachycardia; differentials include vasculitis, migraine change, or less likely demyelination; MRI was negative for parenchymal microhemorrhages, and scattered foci of T2 signaled abnormality in the subcortical and periventricular frontal and parietal white matter; sequencing of the Notch3 gene demonstrated a gain of a cysteine residue within one of the EGF-like repeats of the Notch3 receptor: 499C>T (ARG141CYS); daily treatments and medications: probiotics, fish oil, aspirin, multivitamins and B-complex; family history: proband is daughter of affected mother (not in repository) and has two affected sisters (GM27171 and GM27172, lymphs); mother and maternal uncle (both not in repository) were initially diagnosed with multiple sclerosis, but mother was later tested and found to be positive for CADASIL; mother also had lung cancer with brain metastasis, had mild dementia, decreasing mobility, and progressive weakness and died from complications; both sisters have the same CADASIL mutation, 499C>T (ARG141CYS) in Notch3; one sister (GM27171) experienced recurrent early miscarriages, a stroke, neurologic symptoms and facial paresthesias, and was found to have two mutations, 677C>T and 1298A>C, in the MTHFR gene; sisters have Hashimoto thyroiditis.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

NOTCH3

Chromosomal Location

19p13.12

Allelic Variant 1

p.Arg141Cys; CADASIL

Identified Mutation

ARG141CYS; Autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a progressive disorder of the small arterial vessels of the brain manifest by migraine, strokes, and white matter lesions, with resultant cognitive impairment in some patients.