Brothers’ mild JEB seen affecting teeth, nails, groin: Case study
Genetic analysis reveals both had 'destabilizing' mutation
Two brothers shared a mild but distinct form of junctional epidermolysis bullosa (JEB) that affected the teeth, nails, and groin tissue, a case study reported.
While there were no signs of new blisters, the brothers had chronic lesions characterized by delayed wound healing.
The case study, “A Missense Variant Affecting the N-Terminal Domain of the Laminin-332 β3 Chain Results in a Distinct Form of Junctional Epidermolysis Bullosa With Altered Granulation Tissue Response and No New Blistering: A Second Family Report,” was published in the journal Pediatric Dermatology.
JEB is often caused by mutations in one of three genes — LAMA3, LAMB3, or LAMC2 — that encode components of the protein laminin 332. Because this protein helps hold the layers of skin together, such mutations disrupt laminin 332’s production or function, leading to skin that easily tears and blisters. LAMB3 mutations account for about 70% of JEB cases.
The skin condition is inherited in an autosomal recessive pattern, meaning both parents must pass down a defective copy of one of these disease-causing genes. The disorder has two primary forms: generalized severe JEB and non-generalized severe JEB.
Gene mutation
Generalized severe JEB is evident at or shortly after birth, with widespread blistering covering large areas of the body. It can also affect the digestive tract and the ability to eat and digest food. Milder, non-generalized severe JEB may be limited to the hands, elbows, and feet. Other symptoms may include hair loss, malformed fingernails and toenails, and irregular tooth enamel.
More severe forms are most often due to mutations that compromise protein production, leading to the complete absence of laminin 332, while milder forms are caused by mutations that reduce the protein’s function.
A research team in Italy highlighted the case of two Tunisian brothers who developed a mild form of JEB caused by the same mutation that impaired laminin 332’s function.
Upon examination, the researchers found involvement in the teeth, fingers, toes, and groin.
The patients were missing several permanent teeth, the enamel on the remaining teeth was severely malformed, and the brothers had gum inflammation (periodontitis/gum disease).
There were signs of acrocyanosis, in which the hands and feet turn bluish, white, or gray. Multiple fingers showed paronychia, a swelling around the fingernails typically caused by an infection. A complication of paronychia called onychodystrophy, marked by distorted, brittle, and discolored fingernails, was noted, and the brothers’ toenails were malformed, with the nails on the big toe missing.
The brothers each had several chronic ulcerative lesions in the groin region characterized by excessive granulation tissue, which is new tissue that forms on the surfaces of wounds during the healing process. There were no signs of new blister formation.
Genetic analysis revealed that both brothers carried the same mutation (homozygous) in each of their LAMB3 gene copies, one inherited from each biological parent, called p.Gly254Asp.
A computer analysis that estimated protein stability suggested that this mutation had a “highly destabilizing effect” on the laminin 332’s protein structure, the researchers wrote.
The brothers were otherwise healthy, apart from some dental issues. Their parents were first cousins. The cases represented the second Tunisian family reported with this same mutation, the researchers noted.
“The newly reported family confirmed the association of the homozygous p.Gly254Asp variant with a distinct form of JEB, characterized by the absence of new blistering and skin lesions mainly localized in the [groin] region, delayed wound healing and dental anomalies,” the researchers wrote.
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