A novel APC mutation identified in a large Chinese family with familial adenomatous polyposis and a brief literature review.

Familial adenomatous polyposis (FAP), an autosomal dominant disease, is a colon cancer predisposition syndrome that manifests as a large number of adenomatous polyps. Mutations in the Adenomatous polyposis coli (APC) gene are responsible for the majority of cases of FAP. The purpose of the present study was to report the clinical features of a Chinese family with FAP and screen for novel mutations using the targeted next­generation sequencing technology. Among the 29 family members, 12 were diagnosed of FAP. Based on an established filtering strategy and data analyses, along with confirmation by Sanger sequencing and co­segregation, a novel frameshift mutation c.1317delA (p.Ala440LeufsTer14) in exon 10 of the APC gene was identified. To the best of our knowledge, this mutation has not been reported prior to the present study. In addition, it was correlated with extra­colonic phenotypes featuring duodenal polyposis and sebaceous cysts in this family. This novel frameshift mutation causing FAP not only expands the germline mutation spectrum of the APC gene in the Chinese population, but it also increases the understanding of the phenotypic and genotypic correlations of FAP, and may potentially lead to improved genetic counseling and specific treatment for families with FAP in the future.

Steatocystoma multiplex is associated with the R94C mutation in the KRTl7 gene.

Steatocystoma multiplex (SM) is an uncommon disorder, characterized by numerous skin­colored subcutaneous cysts. A number of SM pedigrees have been identified with mutations in the keratin 17 (KRT17) gene. The present study examined a four­generation Chinese pedigree with an autosomal dominant mode of inheritance and examined its genetic basis. A review of the literature on KRT17 gene mutations in the SM pedigree was also performed to investigate the KRT17 gene mutation and genotype­phenotype correlation. Exon 1 of the KRTl7 gene was amplified using polymerase chain reaction (PCR) from genomic DNA obtained, which was obtained from 25 family members in the selected Chinese pedigree and from 100 unrelated control individuals. The DNA was then subjected to automatic DNA sequencing. Genealogical investigations demonstrated an autosomal dominant pattern, and direct sequencing of the PCR product revealed a heterozygous mutation, c.280C/T (R94C), which was located in exon 1 of the KRT17 gene in all 10 affected family members. The mutation was not identified in the 15 unaffected family members or in the 100 unrelated control individuals. Therefore, the present study identified a causative mutation in the KRT17 gene in a large Chinese SM pedigree, exhibiting autosomal dominance. A review of the literature suggested that, in addition to the mutation factor, other modifying factors contribute to the phenotype of familial SM.

Multiple cystic disease: K17 dysfunction?

Our patient is a 29-year-old woman without any previous disease who presented with different kinds of lesions on her face, neck, and chest. She first noticed the lesions 10 years ago and, since that time, they have become more numerous. She has no affected relatives. On physical examination, she had multiple cystic lesions on her neck, chest, and vulva, which were between 0.3 cm and 1 cm and skin-colored or yellowish (Figure 1). She presented with small, white papules on her face measuring approximately 0.2 cm, localized on her forehead and cheeks. Some of these papules had a blueish appearance (Figure 2). She also presented clinically typical eruptive syringomas on her upper and lower eyelids and neck and multiple facial milia. Finally, a sacrococcygeal pilonidal cyst was diagnosed and surgically removed. Her nails and teeth were clinically normal. Biopsies of each kind of lesion were performed, with the following results: (1) neck cystic lesion: steatocystoma; (2) small, white facial papule: eccrine hidrocystoma; (3) blueish facial papule: apocrine hidrocystoma; and (4) small neck papule: syringoma (Figure 3). With these findings, our diagnosis was steatocystoma multiplex with multiple eccrine and apocrine hidrocystomas, eruptive syringomas, and sacrococcygeal pilonidal cyst.

Acral subcutaneous steatocystoma multiplex: a distinct subtype of the disease?

Steatocystoma multiplex (SM) is a hamartomatous malformation of the pilosebaceous duct consisting of dermal cysts filled with a sebum-like material. SM lesions are typically located in areas with sebaceous follicles, although atypical presentations involving sites lacking sebaceous follicles have exceptionally been described. We reviewed retrospectively a series of 32 histologically diagnosed SM observed in our department in the period 2006-2010, evaluating the kinds of lesions and their locations, and family history of SM and associated disorders, to focus on the clinical features of the acral subcutaneous variety of SM and to estimate its prevalence. We found five patients (four women and one man) with asymptomatic deep, skin-colored nodules on the flexor surfaces of distal upper extremities with a mean age at diagnosis and at disease onset of 32.5 and 26 years, respectively. The prevalence was 15%. All five cases were sporadic. The male patient had eruptive syringomas as an associated condition, together with a family history of this tumour. Acral subcutaneous SM may represent a distinct disease variety by virtue of its distinctive clinical features. Dermatologists should be aware of this form, which has to be included in the wide panel of diseases involving subcutaneous tissue.