Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients.

BACKGROUND: Papillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1-4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans. METHODS: To understand the basis of PLS in Mexicans, the gene expression, enzymatic activity and mutational analysis of CTSC were assayed in nine PLS patients and their relatives. Frequencies of CTSC gene polymorphisms and HLA alleles were determined in these patients, their relatives, and the population. RESULTS: Patients showed normal CTSC gene expression, but a deep reduction (up to 85%) in enzymatic activity in comparison to unrelated healthy individuals. A novel loss-of-function mutation, c.203 T > G (p.Leu68Arg), was found in all patients, and some carried the polymorphism c.458C > T (p.Thr153Ile). Allelic frequencies in patients, relatives and controls were 88.89%, 38.24% and 0.25% for G (c.203 T > G); and 11.11%, 8.82% and 9.00% for T (c.458C > T). HLA-DRB1*11 was found significantly more frequent (P = 0.0071) in patients than controls (33.33% vs. 7.32%), with an estimated relative risk of 6.33. CONCLUSIONS: The novel loss-of function mutation of CTSC gene (c.203 T > G) found in patients correlated with their diminished enzymatic activity, and HLA-DRB1*11 was found to be associated with PLS. The study of more PLS patients may give more insights into the etiology of the disease as well as its prevalence in México.

The leprosy agents Mycobacterium lepromatosis and Mycobacterium leprae in Mexico.

BACKGROUND: Mycobacterium leprae was the only known cause of leprosy until 2008, when a new species, named Mycobacterium lepromatosis, was found to cause diffuse lepromatous leprosy (DLL), a unique form of leprosy endemic in Mexico. METHODS: We sought to differentiate the leprosy agents among 120 Mexican patients with various clinical forms of leprosy and to compare their relative prevalences and disease features. Archived skin biopsy specimens from these patients were tested for both M. leprae and M. lepromatosis using polymerase chain reaction-based species-specific assays. RESULTS: Etiologic species were confirmed in 87 (72.5%) patients, of whom 55 were infected with M. lepromatosis, 18 with M. leprae, and 14 with both organisms. The endemic regions of each agent differed but overlapped. Patients with M. lepromatosis were younger and were distributed across more states; their clinical diagnoses included DLL (n = 13), lepromatous leprosy (LL) (n = 34), and eight other forms of leprosy. By contrast, the diagnoses of patients with M. leprae did not include DLL but did include LL (n = 15) and three other forms of leprosy. Thus, M. lepromatosis caused DLL specifically (P = 0.023). Patients with M. lepromatosis also showed more variable skin lesions; the extremities were the most common sites of biopsy in these patients. Finally, patients with dual infections manifested all clinical forms and accounted for 16.1% of all species-confirmed cases. CONCLUSIONS: Mycobacterium lepromatosis is another cause of leprosy and is probably more prevalent than M. leprae in Mexico. It mainly causes LL and also specifically DLL. Dual infections caused by both species may occur in endemic areas.

Tetralogy of Fallot associated with macrocephaly-capillary malformation syndrome: a case report and review of the literature.

INTRODUCTION: Macrocephaly-capillary malformation syndrome is characterized by cutaneous vascular lesions, including cutis marmorata telangiectatica and hemangiomas, associated with congenital anomalies, including macrocephaly, macrosomia, asymmetry and mental retardation. In addition to these cardinal signs, several other clinical conditions have been reported in people with this condition. However, to the best of our knowledge, the presence of tetralogy of Fallot has not previously been reported in association with this syndrome. CASE PRESENTATION: We present a case of a Mexican newborn girl with tetralogy of Fallot associated with macrocephaly-capillary malformation. We discuss the clinical treatment of the patient and its consequences. CONCLUSION: Since physiologic cutis marmorata is a common condition in newborns, the information provided in this report could be helpful in future cases in preventing severe clinical consequences or sudden death in patients with similar symptoms.