Skin disease caused by sperm cell transmission of keratin mutation

June 16, 2017, Nagoya University
Epidermolytic nevus (EN) is visible as patches of thickened skin over small areas of the body. Mutations in genes encoding the skin proteins keratin 1 or keratin 10 are responsible for EN, but these mutations only occur in some cell populations of the body, including those of skin lesions, so they are known as mosaic. When the causative mutation occurs in germ cells, it is known as gonadal mosaicism. Birthmarks are not usually inherited because sperm cell genes are rarely mutated. However, when inheritance does occur, the children develop skin symptoms identical to their affected parent but covering their entire body. Credit: Nagoya University

Nagoya University research identified a patient with the whole-body skin disease epidermolytic ichthyosis that had been inherited as a germline mutation from her father with the milder epidermolytic nevus. Analysis of genomic DNA from the patient revealed a mutation in the keratin 10 gene, which was identical to that observed in cells taken from patches of thickened skin on the father's body. Assessing transmission risk of such diseases allows affected couples to receive genetic counseling.

A Nagoya University research collaboration reveals the father–daughter inheritance of a mosaic disease as a sperm cell mutation causing a whole- skin disorder: relevance to .

Birthmarks can be caused by an overgrowth of in the top layer of skin, as in the case of epidermolytic nevus (EN), which is visible as patches of thickened skin over small areas of the body. Mutations in genes encoding the skin proteins keratin 1 or keratin 10 are responsible for EN, but these only occur in some cell populations of the body so they are known as mosaic. Birthmarks are not usually inherited because the genes of sperm and cells are rarely mutated. However, when inheritance does occur, the children develop skin symptoms identical to their affected parent but covering their entire body.

Research at Nagoya University in collaboration with Juntendo University Urayasu Hospital has led to the identification of one such case of EN in a father that was transmitted to his daughter as a sperm cell (germline) mutation, resulting in the more widespread skin disorder epidermolytic ichthyosis (EI), which affects the whole body. The study was reported in the Journal of Investigative Dermatology.

EI symptoms are obvious from birth as skin redness and blistering that completely covers the body. This worsens over time, with the skin becoming scaly and thickened. Nagoya University researchers clinically diagnosed EI in a 2-year-old Japanese girl, and confirmed her diagnosis with the detection of a mutation in the gene encoding keratin 10.

The girl's father had small patches of thickened skin on his hand, abdomen, and groin, affecting just 0.5% of his body surface. "We took a skin sample from one of these areas and identified the identical keratin 10 mutation that we detected in his daughter," co-author Yasushi Suga says. "This confirmed that the same mutation was causative of EN in the father and had been transmitted to the daughter as EI."

The parents of the girl wanted to know the likelihood of their future children being affected by EI, so the research team used a highly sensitive DNA sequencing technique to reveal that 3.9% of the father's semen carried the mutation. However, determining the exact risk of disease transmission requires consideration of the effect that the mutation has on the sperm's ability to fertilize an egg.

"Symptoms of mosaic inherited skin disorders are highly visible so diseases can be identified before the birth of affected children, unlike genetic diseases that don't affect the skin," corresponding author Michihiro Kono says. "This enables the risk of disease transmission to be determined, and couples to undergo genetic counseling."

Explore further: Study finds cause of, and possible cure for, genetic skin disorder

More information: Michihiro Kono et al. A child with epidermolytic ichthyosis from a parent with epidermolytic nevus: risk evaluation of transmission from mosaic to germline, Journal of Investigative Dermatology (2017). DOI: 10.1016/j.jid.2017.04.036

Related Stories

Study finds cause of, and possible cure for, genetic skin disorder

June 1, 2017
Yale scientists have discovered the cause of a disfiguring skin disorder and determined that a commonly used medication can help treat the condition.

Why thick skin develops on palms and soles, and its links to cancer

February 1, 2017
Scientists from Queen Mary University of London have discovered that foot callouses/keratoderma (thickened skin) can be linked to cancer of the oesophagus (gullet), a disease which affects more than 8000 people in the UK ...

Inherited, rare skin disease informs treatment of common hair disorders, study finds

June 8, 2017
It is almost axiomatic in medicine that the study of rare disorders informs the understanding of more common, widespread ailments. Researchers from the Perelman School of Medicine at the University of Pennsylvania who study ...

Uncovering the biology of a painful and disfiguring pediatric disease

June 12, 2017
Hyaline Fibromatosis Syndrome (HFS) is a rare but severe genetic disease that affects babies, children, and adults. A glassy substance called hyaline accumulates in the skin and various organs of patients, causing painful ...

Scientists discover genetic mutation that causes rare skin disease keratolytic winter erythema

May 5, 2017
Scientists have discovered the genetic mutation that causes the rare skin disease, keratolytic winter erythema (KWE), or 'Oudtshoorn skin', in Afrikaners.

Recommended for you

Advance genetics study identifies virulent strain of tuberculosis

May 22, 2018
LSTM's Dr. Maxine Caws is co-lead investigator on an advanced genetics study published in Nature Genetics, which has shown that a virulent strain of tuberculosis (TB) has adapted to transmit among young adults in Ho Chi Minh ...

Cell types underlying schizophrenia identified

May 22, 2018
Scientists at Karolinska Institutet in Sweden and University of North Carolina have identified the cell types underlying schizophrenia in a new study published in Nature Genetics. The findings offer a roadmap for the development ...

Researchers discover cell structure that plays a role in epigenetic inheritance

May 22, 2018
We know a lot about how genes get passed from parent to child, but scientists are still unraveling how so-called epigenetic information—instructions about which genes to turn on and off—is conveyed from generation to ...

New data changes the way scientists explain how cancer tumors develop

May 21, 2018
A collaborative research team has uncovered new information that more accurately explains how cancerous tumors grow within the body. This study is currently available in Nature Genetics.

Researchers identify genetic variants that may predict glaucoma risk

May 21, 2018
A study led by scientists from King's College London, University College London, Massachusetts Eye and Ear and Harvard Medical School has identified 133 genetic variants that could help predict the risk of developing glaucoma, ...

Team identifies new mechanism essential for eye lens development

May 17, 2018
If you want to take clear photographs, you don't use sandpaper to clear a smudge from your camera's lens. Similarly, if you want to see clearly, the lens of your eye has to be free of obstruction.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.