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Expanding the phenotype of DST ‐related disorder: A case report suggesting a genotype/phenotype correlation
Author(s) -
Cappuccio Gerarda,
Pinelli Michele,
Torella Annalaura,
Alagia Marianna,
Auricchio Renata,
Staiano Annamaria,
Nigro Vincenzo,
BrunettiPierri Nicola
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38367
Subject(s) - exon , phenotype , gene isoform , biology , genetics , epidermolysis bullosa simplex , genodermatosis , gene , exon trapping , alternative splicing , allele , mutation , allelic heterogeneity , microbiology and biotechnology
The gene DST encodes for the large protein BPAG1 involved in hemidesmosomes. Its alternative splicing gives rise to tissue‐enriched isoforms in brain, muscle, and skin. The few patients described so far with bi‐allelic mutations in the DST gene have either a skin phenotype of epidermolysis bullosa simplex or a neurological phenotype. Here, we report a 17‐year‐old female individual presenting with a more complex phenotype consisting of both skin and neuronal involvement, in addition to several previously unreported findings, such as iris heterochromia, cataract, hearing impairment, syringomyelia, behavioral, and gastrointestinal issues, osteoporosis, and growth hormone deficiency. Family‐trio whole exome sequencing revealed that she was a compound heterozygous for two variants in the DST gene with highly‐predicted functional impact, c.3886A>G (p.R1296X) in exon 29 and c.806C>T (p.H269R) in exon 7. Interestingly, exon 7 is included in the neuronal isoform whereas exon 29 is expressed in both skin and neuronal isoforms. The patient we described is the first case with a mutation affecting an exon expressed in both the neuronal and skin isoforms that can explain the more complex phenotype compared to previously reported cases.