GM20735

GM20735 LCL from B-Lymphocyte

Description:

SMITH-MAGENIS SYNDROME; SMS
RETINOIC ACID-INDUCED GENE 1; RAI1

Affected:

Yes

Sex:

Female

Age:

11 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Chromosome Abnormalities

Class

Disorders of the Nervous System

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Possibly Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

ISCN

46,XX.ish 17p13.3(LISIX2),17p11.2(FLIX2)

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; born at 42 weeks gestation; birth weight = 4.1 kg; behavior problems noted at age 9 months with explosive tantrums; frequent irritability with sleep disturbance in infancy; microcephaly diagnosed as an infant (head circumference < 5th percentile) but head growth gradually improved to normal range; height and weight remained at 25th percentile throughout early childhood with gradual increases over time; sat at age 6 months; walked at age 12 months; speech was delayed and regressed at age 4 years with onset of seizures; seizures were complex and involved grand mal, Jacksonian, and petit mal episodes; language, psychosocial, motor, and cognitive skills below the 7th percentile; IQ = 57 on Wechsler scale; self-hugging; attention seeking; head banging; twirling of objects; onychotillomania; polyembolokoilamania of rectum, umbilicus, ears, and mouth; no abnormal sleep patterns at age 11 years (but sedated as a component of seizure therapy); at age 11 years, height and weight about 75th percentile and head circumference at 50th percentile; flat occiput and round face (like mother's); no midface hypoplasia; full lips with tenting of upper lip; multiple small, nonpigmented papillae on tongue; two 2x3 cm cafe-au-lait spots on trunk; eczema behind ears; brachycephaly; no synophrys; brachydactyly; hoarse, deep voice; no recurrent ear infections; hypotonia; no myopia, strabismus, or iris abnormalities; no structural cardiovascular or renal anomalies; EEG showed 2.5-5 Hz delta activity with medium to high amplitude spikes, sharps and polyspikes seen over the right central parietal, right occipital and bifrontal regions; MRI showed slight asymmetry in the gyral sulcation pattern along the left posterior frontal lobe in the precentral gyrus; normal karyotype; no evidence of 17p11.2 deletion; donor subject has a de novo A>G transition at nucleotide 4685 in exon 3 of the RAI1 gene [4685A>G] resulting in a substitution of arginine for glutamine at codon 1562 [Gln1562Arg (Q1562R)].

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

RAI

Chromosomal Location

17p11.2

Allelic Variant 1

Q1562R; SMITH-MAGENIS SYNDROME

Identified Mutation

GLN1562ARG

Phenotypic Data

Remarks

Publications

Girirajan S, Elsas LJ 2nd, Devriendt K, Elsea SH, RAI1 variations in Smith-Magenis syndrome patients without 17p11.2 deletions. J Med Genet42(11):820-8 2005

PubMed ID: 15788730