GM29966

GM29966 Fibroblast from Skin, Skin

Description:

MANNOSIDOSIS, BETA A, LYSOSOMAL; MANSB
MANNOSIDASE, BETA A, LYSOSOMAL; MANBA

Affected:

Yes

Sex:

Male

Age:

7 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
PIGI Consented Sample

Biopsy Source

Skin

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Skin

Subject Type

trio

Family Type

NUCLEAR FAMILIES - ONE AFFECTED

Ethnicity

Hispanic/Latino

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

See "Phenotypic Data" tab. LCL is GM29965. Unaffected father, who is a carrier of the gene is GM29971 (LCL) and GM29972 (Fibro). Unaffected mother, who is a carrier of the gene is GM29973 (LCL) and GM29974 (Fibro).

Characterizations

PDL at Freeze

4.65

Passage Frozen

Gene

LOXHD1

Chromosomal Location

18q21.1

Allelic Variant 1

Thr1962Met; DEAFNESS, AUTOSOMAL RECESSIVE 77; DFNB77

Identified Mutation

c.5885 C>T p.(Thr1962Met)

Gene

MANBA

Chromosomal Location

4q24

Allelic Variant 1

; MANNOSIDOSIS, BETA A, LYSOSOMAL; MANSB

Identified Mutation

c.550-1 G>A p.?

Gene

MANBA

Chromosomal Location

4q24

Allelic Variant 1

Phe188Val; MANNOSIDOSIS, BETA A, LYSOSOMAL; MANSB

Identified Mutation

c.562 T>G p.(F188V)

Gene

MYO7A

Chromosomal Location

11q13.5

Allelic Variant 1

A601T;

Identified Mutation

c.1801 G>A p.(A601T)

Gene

WFS1

Chromosomal Location

4p16.1

Allelic Variant 1

G213E;

Identified Mutation

c.638 G>A p.(G213E)

Phenotypic Data

Demographic Data

Relation to Proband

proband

Age at Sampling

7 YR

Sex

Male

Age at Diagnosis(If not a control)

7 YR

Hispanic or Latino/Not Hispanic or Latino

Hispanic/Latino

Country

USA

Data Elements

Clinical Element Type: General NIGMS Catalog Remarks

(Baseline)

Mutation Information

Gene, variant, consequence, and exon number:

MANBA, C.550-1 G>A P.?, IN INTRON 4, MATERNALLY INHERITED.

Zygosity:

Heterozygous

Other variants:

MANBA, C.562 T>G P.(PHE188VAL) IN EXON 5, HETEROZYGOUS, PATERNALLY INHERITED. LOXHD1, C.5885 C>T P.(THR1962MET) IN EXON 38, HETEROZYGOUS, PATERNALLY INHERITED. MYO7A C.1801G>A (P.ALA601THR), VARIANT OF UNCERTAIN SIGNIFICANCE. WFS1 C.638G>A (P.GLY213GLU), VARIANT OF UNCERTAIN SIGNIFICANCE. HOMOZYGOUS FOR THE C ALLELE OF THE C677T POLYMORPHISM IN THE MTHFR GENE. BDP1 C.4096 C>A P.(P1366T), VARIANT OF UNCERTAIN SIGNIFICANCE. CACNA1D, C.6528DUP P.(C2177MFS*35), VARIANT OF UNCERTAIN SIGNIFICANCE. CDH23, C.3436 C>A P.(H1146N), VARIANT OF UNCERTAIN SIGNIFICANCE. CLDN14, C.424 G>A P.(D142N), VARIANT OF UNCERTAIN SIGNIFICANCE.

Age of Symptom Onset and Age at Diagnosis

Age at Diagnosis:

7 YEARS OLD

In Utero History Information

Additional Information:

FETAL ULTRASOUND NORMAL

Birth History Information

Failure to thrive

Dysmorphic Features

Additional Information:

SHORT STATURE; THIN STATURE.

Neurological Symptoms

Optical and Audiological Symptoms

Defective hearing

Additional Information:

SENSORINEURAL HEARING LOSS, BILATERAL.

Musculoskeletal Symptoms

Additional Information:

NASAL SEPTUM DEVIATED TO THE LEFT.MILD HYPERTROPHY OF NASAL TURBINATES.

Developmental Milestones

Delayed speech and language development
Global developmental delay

Gastrointestinal Symptoms

Constipation

Additional Information:

CHRONIC MALNUTRITION, CHRONIC FEEDING DIFFICULTIES.

Genitourinary Symptoms

Respiratory and Cardiovascular Symptoms

Additional Information:

ALLERGIC RHINITIS DUE TO POLLEN, CAT AND DOG HAIR.

Cognitive and Behavioral Symptoms

Aggression
Attention deficit hyperactivity disorder

Additional Information:

COGNITIVE IMPAIRMENT

Additional Information

Testing Performed

Optical and Audiological Testing:

FAILED NEWBORN HEARING SCREEN. AMBLYOPIA SUSPECT BILATERAL.

Musculoskeletal and Developmental Testing:

XR BONE AGE STUDY: SKELETAL MATURITY NORMAL.

Metabolic, Hematologic, and Endocrinologic Testing:

OLIGOSACCHARIDE URINE ANALYSIS: HEX1HEXNAC1 FREE OLIGOSACCHARIDE IS SIGNIFICANTLY ELEVATED AND CONSISTENT WITH DX OF BETA-MANNOSIDOSIS. DRIED BLOOD SPOT, BETA-MANNOSIDASE: LOW 0.00 NMOL/ML BLOOD/HR, REFERENCE RANGE |13.0-71.0]

Uncategorized Testing:

NORMAL MALE KARYOTYPE.

Treatments and Assistive Devices

Occupational therapy

Medications

QELBREE 150MG ORAL CAPSULE, EXTENDED RELEASE. DIGESTIVE ENZYMES/ HYOSCYAMINE/PHENYLTOLOXAMIN (TWICE A DAY). MULTIVITAMIN; DIVINE NATURE SUPPLEMENTS, FAT SUGAR ENYZYMES, NORDIC OMEGA 3 SUPPLEMENT PREVIOUSLY ON: CYPROHEPTADINE 2MG/5 ML (ONCE A DAY) AND METHYLPHENIDATE 10MG (TWICE A DAY). LACTULOSE 10G /15ML (ONCE A DAY).

Family History

FATHER HAS HISTORY OF ASTHMA, ENVIRONMENTAL ALLERGIES, DIABETES AND HYPERLIPIDEMIA. MOTHER HAS HISTORY OF ANXIETY, PSYCHIATRIC ILLNESS AND DEPRESSION. MOTHER AND FATHER BOTH STARTED WEARING GLASSES YOUNG.

Remarks