GM25580

GM25580 LCL from B-Lymphocyte

Description:

POTOCKI-LUPSKI SYNDROME; PTLS
CATION CHANNEL, AMILORIDE-SENSITIVE, NEURONAL, 1; ACCN1

Affected:

Yes

Sex:

Male

Age:

17 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Chromosome Abnormalities
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

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Confirmation

Karyotypic analysis and Case history

ISCN

46,XY[24].arr[hg19] 17p12p11.2(13,455,944-22,159,899)x3, 17q11.2q12(31,571,037-32,603,721)x1

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected with severe phenotype; pre-natal period complicated by maternal exposure to parvovirus B19, followed by delivery at 36 weeks; post-natal period involved neonatal unconjugated hyperbilirubinemia and paresis of the right leg (due to thoracolumbar syrinx detected by MRI); early infancy involved feeding difficulties, hypotonia, and poor weight gain; diagnosed with oropharyngeal dysphagia under nasogastric intubation until 6 months of age; constipation; at 1 year old, received shunt for syrinx decompression; first steps at 18 months of age; difficulty recognizing faces and following objects at 3-4 years of age; developmental milestones: physical, verbal, social, emotional, and cognitive delay; examination at 7 years of age revealed the following: facial dysmorphisms (prominent forehead, downslanting palpabrel fissures, mild mandibular hypoplasia, triangular face); high arched palate; low-set malformed ears; dental caries; long fingers; hyperextensibility at the elbows and proximal interphalangeal joints; flat arches of feet; bilateral metatarsus adduction; delayed deep tendon reflexes; withdrawal plantar response; weak extremities; truncal hypotonia; mild steppage gait; sensorimotor neuropathy; renal defects (malrotation of left kidney); severe behavioral abnormalities; mental retardation; hyperactivity; moderately severe hearing loss; ophthalmalogic examination revealed severe hyperopia and some amblyopia (subject received refractive correction); sensitive to bright light; perhiperhal nerve biopsy showed reduced packing density with expansion of the intervening endoneurial connective tissue consistent with moderately severe nerve fiber loss; subject diagnosed with malignent hyperthermia (recurrent fevers, anhidrotic, muscle twitching, leukocytosis, and hyperglycemia after general anesthesia); cardiovascular examination showed 3/6 harsh ejection systolic murmur with no diastolic murmur heard; history of congenital heart disease - bicuspid aortic valve, dilated aortic root, ascending aortic aneurysm, patent foramen ovale, ventriculoseptal defect, mild mitral regurgitation, left ventricular hypertrophy, sinus tachycardia, narrow right coronary artery ostium, and episodic syncope (subject underwent multiple corrective surgeries); had Postural Tachycardia Syndrome, which has since been corrected via heart transplant; non-convulsive seizures: EEG revealed multifocal epileptiform discharges with continuous spike and slow wave activity in sleep and MRI of brain showed patchy white matter abnormalities; sleep studies revealed severe sleep disordered breathing with hypercapnia as well as obstructive and central apnea; subject had tonsilectomy and adenectomy; initial G-banding evaluation revealed a partial duplication of chromosome 17p; FISH confirmed 17p11.2 duplication and 25% mosaicism for tetrasomy 17p11.2p12; aCGH and FISH determined that 17p duplication encompasses approximately 7.5 Mb (from COX10 to KCNJ12); aCGH also identified approximately 830 Kb deletion of 17q11.2q12, including exon 1 of ACCN1; subject noted as SMS224 in publication by Girirajan et al (Clin Genet. 2007; PMID: 17594399); history of miscarriages on maternal side; family history of cardiovascular manifestation on maternal and paternal sides (sister had dilated aorta, half-sister had dilated aorta and long QT syndrome, cousin had aortic rupture, etc.); family in the repository include: mother (GM25581), father (GM25582), brother (GM25583), and sister (GM25592).

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

ACCN1

Chromosomal Location

17q11-q12

Allelic Variant 1

;

Identified Mutation

Del Exon1

Phenotypic Data

Remarks

Publications

Girirajan S, Williams S, Garbern J, Nowak N, Hatchwell E, Elsea S, 17p112p12 triplication and del(17)q112q12 in a severely affected child with dup(17)p112p12 syndrome Clinical genetics72:47-58 2007

PubMed ID: 17594399