Identification of novel homozygous SLURP1 mutation in a Javanese family with Mal de Meleda.

BACKGROUND: Mal de Meleda (OMIM# 248300; keratosis palmoplantaris transgrediens) is an autosomal recessive form of palmoplantar keratoderma, clinically characterized by sharp demarcated erythema and hyperkeratosis of the palms and soles that progress with age and extend to the dorsal aspects of the hands and feet. The mal de Meleda is caused by mutations in the SLURP1 gene that encodes secreted lymphocyte antigen 6/urokinase-type plasminogen receptor-related protein 1 (SLURP1). To date no reported cases from Indonesia. The aims of the study were to describe the typical features of mal de Meleda cases in a Javanese family in Indonesia and identify the mutation in the ARS B gene which encodes SLURP1. PATIENTS AND METHODS: In this study, three Javanese patients, siblings from nonconsanguineous nonaffected parents, presented with classical symptoms of mal de Meleda. Genetic analysis screening SLURP1 gene was conducted for the specimens from the patients and other family members. RESULTS: A novel homozygous three-nucleotide deletion in exon 3, i.e. c.271-273TCTdel, was identified in the patients. Subcloning and sequencing revealed both parents (I.2 and I.3) and one of the father's siblings (I.1) carry heterozygous c.271-273TCTdel, while the other father's sibling (I.2), the mother's sister (I.4), and a healthy control matched the ethnicity of the family, showing normal sequence of the entire SLURP1. CONCLUSION: This is the first mal de Meleda case of Javanese ethnicity to be documented, and the unique mutation has not previously been reported. The finding supports the notion that despite the rarity, SLURP1 mutation causing mal de Meleda is ubiquitous.

Ferrochelatase gene mutation in Singapore and a novel frame-shift mutation in an Asian boy with erythropoietic protoporphyria.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disorder of heme biosynthesis caused by decreased activity of the enzyme ferrochelatase (FECH ). The frequency of the hypomorphic c.333-48C allele in a population directly contributes to the prevalence of EPP in the same population. This study sought to identify the molecular basis of EPP in a Chinese patient from Singapore and the c.333-48C allele frequency among the Chinese population in Singapore. MATERIALS AND METHODS: FECH gene was screened for mutation in the patient's DNA sample by polymerase chain reaction amplification and DNA sequencing. To validate the identified mutation, the FECH region harboring the mutation was screened in DNA samples from all healthy controls. One patient and 46 ethnically matched healthy controls were included in the study. RESULTS: A novel c.474dupC which leads to a frameshift and premature stop codon was identified in one allele, while the other allele showed to carry c.333-48C and c.337C>T variants in the patient's FECH. The frequency of the c.333-48C hypomorphic allele is 27% among Chinese population in Singapore. CONCLUSIONS: c.474dupC in one allele trans to hypomorphic c.333-48C and c.337C>T allele in FECH gene may be the underlying cause of the clinical EPP of the studied patient. The FECH hypomorphic c.333-48C allele frequency in Singapore is lower than the Han Chinese (41.3%) and Japanese (43%) populations but nearly the same as the Southeast Asian (31%) population and higher than the European (2.7-11%) population.

Complementary role of a polymerase chain reaction test in the diagnosis of onychomycosis.

BACKGROUND: The successful treatment of onychomycosis depends on accurate diagnosis. Conventional diagnostic methods, including direct microscopy and fungal culture, are non-specific, insensitive and time-consuming. Recently, PCR has shown promise in improving the diagnosis of onychomycosis. We aimed to evaluate a commercially available PCR kit for the in vitro detection of dermatophytes and specifically Trichophyton rubrum in nail specimens with suspected onychomycosis, and to compare the detection rates of PCR with conventional diagnostic methods. METHODS: Nail specimens were prospectively collected from patients with clinically suspected onychomycosis. All nail specimens were positive on direct microscopic examination. PCR and fungal cultures were administered, and the detection rates of dermatophytes were compared. RESULTS: In all, 107 nail specimens were analysed. The fungal culture was positive in 57 (53%) specimens (38 dermatophytes and 19 non-dermatophytes). PCR was positive in 77 (72%) specimens (63 T. rubrum and 14 pan-dermatophyte). A total of 37 specimens (35%) were positive for both fungal culture and PCR. PCR detected dermatophytes in 39 specimens that were missed by the fungal culture, increasing the diagnosis of dermatophyte-positive specimens by 37%. Five dermatophyte-culture-positive specimens were negative for PCR. CONCLUSIONS: This study demonstrates that PCR increases the sensitivity of detection of dermatophytes in nail specimens. Despite its limitations, the use of PCR can complement direct microscopic examination and fungal cultures to aid clinicians in the diagnosis of suspected dermatophytic onychomycosis.

Acroangiodermatitis of Mali in protein C deficiency due to a novel PROC gene mutation.

Acroangiodermatitis of Mali is a dermatologic condition of kaposiform skin lesions that has been associated with chronic venous insufficiency. Here we report a case of a 28-year-old Chinese man with acroangiodermatitis which co-existed with chronic lower limb deep vein thrombosis. Investigations revealed protein C deficiency and a frame shift mutation, c246_247dupCT, of the PROC gene. Our report lengthens the list of male acroangiodermatitis of Mali cases with a Chinese patient harboring a novel PROC mutation with manifest protein C deficiency.

Characterization of a novel S13F desmin mutation associated with desmin myopathy and heart block in a Chinese family.

Desmin myopathy was identified in a Chinese man with complete heart block and mild proximal and distal limb weakness. A novel heterozygous missense S13F mutation of the desmin gene was found to be associated with the myopathy. Family members carrying the mutation showed a similar or milder phenotype. The mutation is located at a protein kinase-C phosphorylation site within a highly conserved nonapeptide sequence in the head domain of the desmin protein. Expression of the mutant desmin cDNA in cell lines induced large desmin accumulations associated with preservation of a filamentous network.

A novel transthyretin mutation V32A in a Chinese man with late-onset amyloid polyneuropathy.

We report a Chinese patient with amyloidotic polyneuropathy associated with a novel transthyretin mutation (V32A). He presented with slowly progressive sensorimotor polyneuropathy accompanied by autonomic dysfunction and cardiomyopathy by echocardiography. This mutation is likely to be associated with late onset and low-penetrance phenotype.