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Rubinstein–Taybi Syndrome (RSTS) is a rare congenital disease with distinctive facial features, broadening of the thumbs and halluces, and developmental delay. RSTS is caused by de novo genetic alterations in CREBBP and the homologous EP300 genes. In this study, we established a genetic diagnostic protocol by integrating multiplex ligation-dependent probe amplification (MLPA) and whole-exome sequencing (WES). Five patients clinically diagnosed with RSTS were enrolled for genetic testing. Germline DNA was extracted from the peripheral blood of the patients and their families. One patient (case 1) was identified as harboring a large heterozygous deletion in the 16p13.3 region, spanning the CREBBP gene. Three patients (Cases 2–4) harbored different CREBBP variants (c.2608C>T:p.Gln870Ter,c.4404_4405del:p.Thr1468fs,c.3649C>T:p.Gln1217Ter). No causative variants were identified for the fifth RSTS patient (case 5). Here, we propose a molecular diagnostic protocol that identified causative genetic alterations in 4/5 of the patients, yielding a molecular diagnostic rate of 80%. Given the rarity of RSTS, more research is needed to explore its pathogenesis and mechanism.

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Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare type of epidermal nevus involving the eccrine acrosyringia. It typically presents as asymptomatic linear keratotic papules and plaques along the lines of Blaschko and predominantly affects the extremities. This disease has recently been linked to somatic mutations within the GJB2 locus. Only four GJB2 mutations have been previously documented for PEODDN, and the underlying genetic basis remains inconclusive. Herein, we report an 18‐year‐old female with a hyperkeratotic plaque on the dorsa of the proximal interphalangeal joint of her right ring finger, as well as multiple small hyperkeratotic papules linearly distributed on the lateral sides of her fingers occurring since birth. Histopathological results revealed prominent parakeratotic cornoid lamella‐like tiers at the opening of the eccrine secretory ducts. Whole‐exome sequencing of the affected skin tissue revealed a heterozygous germline mutation and a postzygotic somatic mutation in GJB2. In summary, this study presents a case of PEODDN with compound heterozygous mutations in GJB2, which broadens the genetic spectrum of this disease entity and implies a possible role for second‐hit mutations in the pathogenesis of PEODDN.