GM27650

GM27650 Fibroblast from Skin, Arm

Description:

SCHUURS-HOEIJMAKERS SYNDROME; SHMS

Affected:

Yes

Sex:

Female

Age:

15 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
PIGI Consented Sample

Biopsy Source

Arm

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Arm

Race

White

Ethnicity

Not Hispanic/Latino

Ethnicity

Irish, German and Swedish

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Species

Homo sapiens

Common Name

Human

Remarks

See Phenotypic Data Tab; both parents are non-carriers for the mutation in PACS1; mother is GM27651 (fibro).

Characterizations

PDL at Freeze

5.87

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by LINE assay

Gene

PACS1

Chromosomal Location

11q13.1-q13.2

Allelic Variant 1

607492.0001; SCHUURS-HOEIJMAKERS SYNDROME

Identified Mutation

R203W (c.607C>T); In 2 unrelated boys with mental retardation and a strikingly similar facial appearance (SHMS; 615009), Schuurs-Hoeijmakers et al. (2012) identified a recurrent de novo mutation in the PACS1 gene, resulting in a missense mutation (R203W; 607492.0001) in the furin (cargo) binding region directly adjacent to the CK2 binding motif. Schuurs-Hoeijmakers et al. (2012) found that altered PACS1 forms cytoplasmic aggregates in vitro with concomitant increased stability and showed impaired binding to an isoform-specific variant of TRPV4 (605427), but not the full-length protein.

Phenotypic Data

Demographic Data

Relation to Proband

proband

Age at Sampling

15 YR

Sex

Female

Age at Diagnosis(If not a control)

10 YR

Hispanic or Latino/Not Hispanic or Latino

Not Hispanic/Latino

Racial Category

White

Country

USA

Data Elements

Clinical Element Type: General NIGMS Catalog Remarks

(Baseline)

Mutation Information

Gene, variant, consequence, and exon number:

WHOLE EXOME SEQUENCING REVEALED A DE NOVO HETEROZYGOUS AUTOSOMAL DOMINANT MUTATION IN THE PACS1 GENE: C.607C>T (CGG>TGG, P.R203W)

Zygosity:

Heterozygous

Age of Symptom Onset and Age at Diagnosis

Age of Symptom Onset:

BIRTH

Age at Diagnosis:

In Utero History Information

Birth History Information

Dysmorphic Features

Wide mouth
Hypertelorism
Microcephaly

Additional Information:

DYSMORPHIC FEATURES; BULBOUS NOSE; FLAT PHILTRUM

Neurological Symptoms

Optical and Audiological Symptoms

Additional Information:

BILATERAL RETINAL COLOBOMAS

Musculoskeletal Symptoms

Scoliosis

Additional Information:

SHORT STATURE

Developmental Milestones

Global developmental delay

Additional Information:

NON-VERBAL

Gastrointestinal Symptoms

Genitourinary Symptoms

Respiratory and Cardiovascular Symptoms

Cognitive and Behavioral Symptoms

Additional Information:

INTELLECTUAL DISABILITY

Additional Information

Testing Performed

Treatments and Assistive Devices

Wheelchair or ambulation devices
Orthotics
Communication or learning devices

Additional Testing:

SURGERIES: EAR TUBES AT 18 MONTHS AND 5 YEARS OF AGE

Medications

ABILIFY, GLYCOLAX, FAMOTIDINE, PROBIOTIC

Family History

PARENTS DO NOT CARRY THE MUTATION IN PACS1.

Publications

Villar-Pazos S, Thomas L, Yang Y, Chen K, Lyles JB, Deitch BJ, Ochaba J, Ling K, Powers B, Gingras S, Kordasiewicz HB, Grubisha MJ, Huang YH, Thomas G, Neural deficits in a mouse model of PACS1 syndrome are corrected with PACS1- or HDAC6-targeting therapy Nature communications14:6547 2023

PubMed ID: 37848409

External Links

NCBI GTR

615009 SCHUURS-HOEIJMAKERS SYNDROME; SHMS

OMIM

615009 SCHUURS-HOEIJMAKERS SYNDROME; SHMS

Culture Protocols

Cumulative PDL at Freeze

5.87

Passage Frozen

Split Ratio

1:3

Temperature

37 C

Percent CO2

Percent O2

AMBIENT

Medium

Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent

Serum

15% fetal bovine serum Not inactivated

Supplement

Pricing

Commercial/For-profit:

$311.00USD

Academic/Non-profit/Government:

$176.00USD