Dystrophic epidermolysis bullosa: 104 mutations found in single gene

 

A total of 104 distinct mutations in a single gene, COL7A1, were discovered in a multiethnic cohort of 152 Iranian families with dystrophic epidermolysis bullosa, according to a report published online in the Journal of Investigative Dermatology.

Identifying which specific mutations in the COL7A1 gene a given patient is carrying should allow clinicians to render a more accurate prognosis and may even dictate management strategies to counteract manifestations of the disease. Dystrophic epidermolysis bullosa (EB) can have an extremely variable progression that depends, in part, on the underlying molecular defects in many different genes expressed in the dermal-epidermal junction, according to study investigators Hassan Vahidnezhad, MD, of the department of dermatology and cutaneous biology, Thomas Jefferson University, Philadelphia, and his associates.

©kgtoh/Thinkstock

“Recent preclinical studies have opened a number of new avenues for potential treatment, and some of these approaches have already entered early clinical trials,” they wrote. The mutation data also can be used to inform prenatal testing and genetic counseling, noted Dr. Vahidnezhad and his colleagues.

The study cohort included many consanguineous marriages, which are customary in Iran as in many parts of the Middle East, North Africa, and sub-Saharan Africa. In addition, many migrant communities from these regions now reside in Western countries and continue to practice these marriage customs, most commonly marriages between first cousins. “It is estimated that globally at least 20% of the human population live in communities with a preference for consanguineous marriage,” the researchers wrote (J Investig Dermatol. 2016. doi: 10.1016/j.jid.2016.10.023).

Dystrophic epidermolysis bullosa is characterized by blistering of the sublamina densa that leads to erosions; chronic ulcers; and extensive scarring, especially at sites of trauma on the hands and feet. Blistering can also develop in corneal and gastrointestinal epithelium, which adversely affects vision and feeding, and patients often develop aggressive squamous cell carcinoma with its attendant premature mortality.

Dystrophic EB has long been associated with mutations in COL7A1 as well as other genes. COL7A1 encodes type VII collagen, “a major protein component of the anchoring fibrils, which play a critical role in securing the attachment of the dermal-epidermal basement membrane to the underlying dermis.” Many patients with dystrophic EB show marked reductions in, or a total absence of, anchoring fibrils.

The investigators explored COL7A1 mutations in a multiethnic database comprising 238 patients in 152 extended families from different parts of the country. (The approximately 80 million people in Iran include several ethnic groups with distinct ancestries, languages, cultures, and geographic areas of residence.) A total of 139 of these families were consanguineous.

A total of 104 distinct COL7A1 mutations were detected in 149 of the 152 families, for a detection rate of 98%. Many mutations had been reported previously, but 56 had never been reported before. Approximately 90% of the families in the study cohort showed homozygous recessive mutations, which appears to reflect the consanguinity of this population, Dr. Vahidnezhad and his associates said.

They concluded that “the overwhelming majority” of patients with dystrophic EB carry COL7A1 genes harboring mutations.
 

This study was supported by DEBRA International and the Sidney Kimmel Cancer Center at Thomas Jefferson University. Dr. Vahidnezhad and his associates reported having no relevant financial disclosures.

 

A total of 104 distinct mutations in a single gene, COL7A1, were discovered in a multiethnic cohort of 152 Iranian families with dystrophic epidermolysis bullosa, according to a report published online in the Journal of Investigative Dermatology.

Identifying which specific mutations in the COL7A1 gene a given patient is carrying should allow clinicians to render a more accurate prognosis and may even dictate management strategies to counteract manifestations of the disease. Dystrophic epidermolysis bullosa (EB) can have an extremely variable progression that depends, in part, on the underlying molecular defects in many different genes expressed in the dermal-epidermal junction, according to study investigators Hassan Vahidnezhad, MD, of the department of dermatology and cutaneous biology, Thomas Jefferson University, Philadelphia, and his associates.

©kgtoh/Thinkstock

“Recent preclinical studies have opened a number of new avenues for potential treatment, and some of these approaches have already entered early clinical trials,” they wrote. The mutation data also can be used to inform prenatal testing and genetic counseling, noted Dr. Vahidnezhad and his colleagues.

The study cohort included many consanguineous marriages, which are customary in Iran as in many parts of the Middle East, North Africa, and sub-Saharan Africa. In addition, many migrant communities from these regions now reside in Western countries and continue to practice these marriage customs, most commonly marriages between first cousins. “It is estimated that globally at least 20% of the human population live in communities with a preference for consanguineous marriage,” the researchers wrote (J Investig Dermatol. 2016. doi: 10.1016/j.jid.2016.10.023).

Dystrophic epidermolysis bullosa is characterized by blistering of the sublamina densa that leads to erosions; chronic ulcers; and extensive scarring, especially at sites of trauma on the hands and feet. Blistering can also develop in corneal and gastrointestinal epithelium, which adversely affects vision and feeding, and patients often develop aggressive squamous cell carcinoma with its attendant premature mortality.

Dystrophic EB has long been associated with mutations in COL7A1 as well as other genes. COL7A1 encodes type VII collagen, “a major protein component of the anchoring fibrils, which play a critical role in securing the attachment of the dermal-epidermal basement membrane to the underlying dermis.” Many patients with dystrophic EB show marked reductions in, or a total absence of, anchoring fibrils.

The investigators explored COL7A1 mutations in a multiethnic database comprising 238 patients in 152 extended families from different parts of the country. (The approximately 80 million people in Iran include several ethnic groups with distinct ancestries, languages, cultures, and geographic areas of residence.) A total of 139 of these families were consanguineous.

A total of 104 distinct COL7A1 mutations were detected in 149 of the 152 families, for a detection rate of 98%. Many mutations had been reported previously, but 56 had never been reported before. Approximately 90% of the families in the study cohort showed homozygous recessive mutations, which appears to reflect the consanguinity of this population, Dr. Vahidnezhad and his associates said.

They concluded that “the overwhelming majority” of patients with dystrophic EB carry COL7A1 genes harboring mutations.
 

This study was supported by DEBRA International and the Sidney Kimmel Cancer Center at Thomas Jefferson University. Dr. Vahidnezhad and his associates reported having no relevant financial disclosures.

 

A total of 104 distinct mutations in a single gene, COL7A1, were discovered in a multiethnic cohort of 152 Iranian families with dystrophic epidermolysis bullosa, according to a report published online in the Journal of Investigative Dermatology.

Identifying which specific mutations in the COL7A1 gene a given patient is carrying should allow clinicians to render a more accurate prognosis and may even dictate management strategies to counteract manifestations of the disease. Dystrophic epidermolysis bullosa (EB) can have an extremely variable progression that depends, in part, on the underlying molecular defects in many different genes expressed in the dermal-epidermal junction, according to study investigators Hassan Vahidnezhad, MD, of the department of dermatology and cutaneous biology, Thomas Jefferson University, Philadelphia, and his associates.

©kgtoh/Thinkstock

“Recent preclinical studies have opened a number of new avenues for potential treatment, and some of these approaches have already entered early clinical trials,” they wrote. The mutation data also can be used to inform prenatal testing and genetic counseling, noted Dr. Vahidnezhad and his colleagues.

The study cohort included many consanguineous marriages, which are customary in Iran as in many parts of the Middle East, North Africa, and sub-Saharan Africa. In addition, many migrant communities from these regions now reside in Western countries and continue to practice these marriage customs, most commonly marriages between first cousins. “It is estimated that globally at least 20% of the human population live in communities with a preference for consanguineous marriage,” the researchers wrote (J Investig Dermatol. 2016. doi: 10.1016/j.jid.2016.10.023).

Dystrophic epidermolysis bullosa is characterized by blistering of the sublamina densa that leads to erosions; chronic ulcers; and extensive scarring, especially at sites of trauma on the hands and feet. Blistering can also develop in corneal and gastrointestinal epithelium, which adversely affects vision and feeding, and patients often develop aggressive squamous cell carcinoma with its attendant premature mortality.

Dystrophic EB has long been associated with mutations in COL7A1 as well as other genes. COL7A1 encodes type VII collagen, “a major protein component of the anchoring fibrils, which play a critical role in securing the attachment of the dermal-epidermal basement membrane to the underlying dermis.” Many patients with dystrophic EB show marked reductions in, or a total absence of, anchoring fibrils.

The investigators explored COL7A1 mutations in a multiethnic database comprising 238 patients in 152 extended families from different parts of the country. (The approximately 80 million people in Iran include several ethnic groups with distinct ancestries, languages, cultures, and geographic areas of residence.) A total of 139 of these families were consanguineous.

A total of 104 distinct COL7A1 mutations were detected in 149 of the 152 families, for a detection rate of 98%. Many mutations had been reported previously, but 56 had never been reported before. Approximately 90% of the families in the study cohort showed homozygous recessive mutations, which appears to reflect the consanguinity of this population, Dr. Vahidnezhad and his associates said.

They concluded that “the overwhelming majority” of patients with dystrophic EB carry COL7A1 genes harboring mutations.
 

This study was supported by DEBRA International and the Sidney Kimmel Cancer Center at Thomas Jefferson University. Dr. Vahidnezhad and his associates reported having no relevant financial disclosures.