De Novo COL7A1 mutation in a patient with trisomy 21: coexistence of dystrophic epidermolysis bullosa and Down syndrome.
BACKGROUND
Down syndrome (DS) is the most common autosomal chromosomal disorder. Epidermolysis bullosa (EB) is a rare genodermatosis characterized by skin and mucous membrane fragility, with formation of blisters and erosions after minor trauma. Dystrophic EB (DEB) is inherited as an autosomal dominant (DDEB) or recessive (RDEB) trait. Both forms are caused by mutations in COL7A1, the gene coding for the type VII collagen. We report a patient affected by both conditions: DS and DDEB.


METHODS
A patient with DS developed generalized blisters at the age of three months. Cytogenetic study was performed to confirm DS. Skin biopsies were examined with immunohistochemical and electron microscopy techniques to determine EB subtype. Genomic DNA was extracted from peripheral blood samples. COL7A1 mutations were screened by heteroduplex analysis using conformation-sensitive gel electrophoresis and sequencing.


RESULTS
Karyotype analysis revealed trisomy 21. Histological study agreed with a DEB diagnosis. Mutational analysis showed a heterozygous c.6127G>T mutation in COL7A1, which is compatible with DDEB. Parental study suggests that c.6127G>T arises as a de novo mutation.


CONCLUSIONS
This report demonstrates that EB can be associated with other common conditions and reports the case of a patient who suffered two de novo independent genetic conditions. It also contributes to expanding the knowledge and database of clinical and molecular aspects of DDEB.
Dystrophic Epidermolysis Bullosa Research Association (DEBRA)-Chile. javicatl@gmail.com
Javiera A
JA
Catalán
Fernando A
FA
Rodríguez
María J
MJ
Yubero
Francis
F
Palisson
María J
MJ
Gana
Susanne M
SM
Krämer
Gabriela M
GM
Repetto
D000293:Adolescent; D024143:Collagen Type VII / Q000235:genetics*; D020732:Cytogenetic Analysis; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics; D016108:Epidermolysis Bullosa Dystrophica / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D059785:Karyotype; D008297:Male; D017354:Point Mutation
C569053:COL7A1 protein, human; D024143:Collagen Type VII