Harlequin Ichthyosis

Video: Hunter Steintz

Contact: Fargo March of Dimes

Address: 1712 Main Avenue #101, Fargo, ND, 58103

Phone: (701) 235-5530

Fax: (701) 235-8725

E-mail: ND407@marchofdimes.com

Facebook: https://www.facebook.com/ndmarchofdimes

What's Their Mission?

"We're dedicated to improving the health of ALL babies by preventing birth defects, premature birth, and infant mortality through funding medical research, educational programs, and advocacy.

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Outlook and Quality of Life

Life Expectancy

• Very short lifespan
• Most infants will die within a few days of birth due to systemic infection (affects multiple systems of the body)
• Very difficult life
• Scales make it difficult to bend your arms and legs
• Normal skin forms a barrier that protects from disease and wounds, but this disorder disrupts this barrier and makes it very easy to contract serious illnesses.

Treatments

• No true cure
• Various drugs to relieve dehydration, respiratory problems, infections (due to open skin)
• Retinoids - drugs that regulate epithelial cell growth, improves tissue growth and immune system
• Sterile environment
• Infants are bathed twice per day, with use of wet sodium chloride compresses and moisturizers to soften scaly skin

New Development/Research

• May result in higher life expectancy
• Different genes that cause this disorder may be found in the future
• Technology - humidified incubator for newborns to regulate their body temperatures
• Keeps baby warm and hydrated

Fun Video:

Blame It on The DNA!

Retinoids

References:

Harlequin ichthyosis. (2008, November). Retrieved November 25, 2013, from

Genetics Home Reference website: http://ghr.nlm.nih.gov/condition/

harlequin-ichthyosis

Harlequin ichthyosis. (2013, July 24). Retrieved December 1, 2013, from

http://medicaltreasure.com/harlequin-ichthyosis/

Symptoms & Characteristics of Disease

Who is Affected?

How common is this disorder?

Main Symptoms:

• Infant skin is hard, separated by deep cracks into thick and scaly patches
• Restricts chest movement - leads to respiratory problems
• Restricts most physical movement
• Excessive dehydration of skin

Possible Symptoms (due to pleiotropic gene):

• Hypoplasia - have difficulty grabbing objects with fingers
• Poorly developed ears/nose or no ears/nose
• Everted eyelids (inside out) - may bleed right after birth
• Polydactyly - extra digits
• Impaired heat loss - body temperature changes quickly
• Poor immune system

• Who is affected?
• Autosomal recessive - infants of both genders
• All ethnic groups
• Babies are diagnosed immediately after birth or during infancy
• How common is it? Very rare!
• Why?
• Recessive inheritance - not expressed unless both parents pass on the gene
• Lethal allele - people affected usualy die before reproducing
• Survivors
• Nelly Shaheen - oldest known survivor
• Only 29 years old!
• Hunter Steintz - the only American (out of 12 known) who has survived

Oldest Survivor - Nelly Shasheen

References:

Harlequin ichthyosis. (2013, July 24). Retrieved December 1, 2013, from

http://medicaltreasure.com/harlequin-ichthyosis/

Inheritance

• Mode of Inheritance: autosomal recessive
• Both males and females affected
• Both parents must be carriers and usually show no symptom
• Type of Mutation: missense
• One nucleotide change (point mutation) results in a codon that codes for a different amino acid
• One amino acid replaced by another causes a loss of function of the ABCA12 protein, which affects development of skin

Autosomal Recessive Inheritance Pedigree

Both of those parents must be carriers in order for two of their children to have the disorder.

Chromosome Ideogram

References:

ABCA12 - ATP-binding cassette sub-family A member 12 - human protein. (2011).

Retrieved December 1, 2013, from http://www.nextprot.org/db/entry/NX_Q86UK0

ABCA12 gene. (2013, October 23). Retrieved December 1, 2013, from

http://www.genecards.org/cgi-bin/carddisp.pl?gene=ABCA12

ABCB11*

ABCA12

p arm

q arm

****ABCB11 gene (2q24): causes different types of cholestasis, which impairs bile (a digestive fluid that helps the body process fat) secretion

Mutations of different genes on the SAME chromosome have different results!

• Chromosomal shorthand: 2q34 (long arm of chromosome 2 at position 34)
• Location: base pair 215,796,265 to base pair 216,003,150 (on chromosome 2)

References:

ABCA12. (2008, November). Retrieved November 27, 2013, from Genetics Home

Reference website: http://ghr.nlm.nih.gov/gene/ABCA12

Inside the Cell

Harlequin Ichthyosis

• Gene Name: ATP-binding cassette, sub-family A (ABC1), member 12
• Abbreviation: ABCA12
• # of Base Pairs (DNA Sequence): 9192 Base Pairs
• Chromosome #: 2
• # of Amino Acids (Amino Acid Sequence): 2595 amino acids
• Protein: ATP-binding cassette sub-family A member 12
• AKA: ATP-binding cassette transporter 12
• Function of Protein: a transport protein that transport fats (lipids) to cells that make up the epidermis (outermost layer of skin)
• Name of Disease: Harlequin Ichthyosis

Cytoplasm

# of Amino Acids (Amino Acid Sequence): 2595

Translation

Transcription

Name of Protein: ATP-binding cassette transporter 12 (ABCA12)

Function of Protein: a transport protein that transport fats (lipids) to cells that make up the epidermis (outermost layer of skin)

Mutation: Without the ABCA12 protein, fats will not be transported properly to cells that need them to make their membranes, skin cells will become physically inhibited, and abnormal skin will result

Disease: Harlequin Ichthyosis (Fishscale Disease)

Gene: ABCA12

Chromosome #2

# of Base Pairs (DNA Sequence): 9192

Nucleus

The Cell

References:

ABCA12. (2008, November). Retrieved November 27, 2013, from Genetics Home

Reference website: http://ghr.nlm.nih.gov/gene/ABCA12

Goldsmith, T., & Fuchs-Telem, D. (2013, September 29). Homo sapiens ATP-binding

cassette, sub-family A (ABC1), member 12 (ABCA12), transcript variant 3,

non-coding RNA. Retrieved December 1, 2013, from National Center for

Biotechnology Information website: http://www.ncbi.nlm.nih.gov/nuccore/

NR_103740.1

By: Kelly Tran