Molecular characterization of mucopolysaccharidosis type IVA patients in the Andean region of Colombia.

Colombia has a high prevalence of mucopolysaccharidosis (MPS) type IVA. Nevertheless, data regarding the mutation spectrum for MPS IVA in this population have not been completely characterized. Forty-seven families and 53 patients from seven different Colombian regions were tested for MPS IVA mutations. We compared the sequences with the N-acetylgalactosamine-6-sulfatase (GALNS) reference sequence NM_000512.4, and gene variants were reported. Bioinformatics analysis was performed using SWISS-MODEL. The mutant proteins were generated by homology from the wild-type GALNS 4FDJ template obtained from the PDB database, and visualization was performed using Swiss-PDBViewer and UCSF Chimera. The predictive analysis was run using different bioinformatic tools, and the deleterious annotation of genetic variants was performed using a neural network. We found that 79% and 21% of the cohort was homozygous and compound heterozygous, respectively. The most frequent mutation observed was p.Gly301Cys (78.3% of alleles), followed by p.Arg386Cys (10.4% of alleles). A novel mutation (p.Phe72Ile) was described and classified in silico as a pathogenic variant. This study reveals the mutation spectrum of MPS IVA in Colombia. The high prevalence of the p.Gly301Cys mutation suggests a founder effect of this variant in the Colombian population that causes diseases in the Andean region (via migration). These data can facilitate genetic counseling, prenatal diagnosis, and the design of therapeutic interventions.

Severe Craniofacial Involvement due to Amniotic Band Sequence.

BACKGROUND: Disruptive amniotic band sequence (DABS) is a sporadic, non-familial disorder with unclear etiology. Diagnosis is based on clinical features because there is currently no reliable laboratory diagnostic tests. OBJECTIVE: We describe six cases of DABS with severe craniofacial deformations, three with and three without classical constrictive limb deformation. RESULTS: The craniofacial deformities were delimited by peripheral sharply demarcated scarring. CONCLUSION: When a sharply demarcated linear disruptive craniofacial lesion is observed, DABS should be considered despite the absence of constrictive limb scarring.

The Unique Spectrum of MUTYH Germline Mutations in Colombian Patients with Extracolonic Carcinomas.

Background: Protein MUTYH, encoded by the gene MUTYH, is an important mismatch repair enzyme in the base-excision repair pathway of DNA repair. When genetically altered, different neoplastic conditions can arise. One of the widely known syndromes associated with MUTYH mutations is MUTYH-associated polyposis, a form of familial colorectal cancer syndrome. MUTYH may also be a driver in other familial cancer syndromes, as well as breast cancer and spontaneous cancer cases. However, some controversies about the role of these alterations in oncogenesis remain, especially when affected in a heterozygous way. Most available data on MUTYH mutations are on Caucasian patients. Material and Methods: We analyzed a small cohort of non-Caucasian, Colombian cancer patients with MUTYH germline heterozygous mutations, clinical features suggestive of familial cancer, and extensive genetic studies with no other mutations and without MUTYH-associated polyposis. Conclusion: With this case series, we intended to provide important data for the understanding of MUTYH as a possible driver of familial cancer, even when only heterozygous mutations are found.

New PAX2 Mutation Associated with Polycystic Kidney Disease: A Case Report.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage renal disease in children. Diagnosis by genetic testing has proven challenging due to its genetic and phenotypic heterogeneity, as well as incomplete penetrance. We report a case on a 16-months old female with a history of renal cysts and a PAX2 mutation. CASE PRESENTATION: The patient presented with a prenatal diagnosis of Potter sequence and a postnatal diagnosis of renal cysts. An ultrasound at 20 weeks gestation revealed right renal agenesis and possible left renal dysplasia. Post natal genetic analyses identified a novel mutation in PAX2. CONCLUSION: Cystic kidney disease is often underdiagnosed due to its variable expressivity and wide range of clinical manifestations; PAX2 genetic screening should be considered for all patients with CAKUT.

PHEX Gene Mutation in a Patient with X-Linked Hypophosphatemic Rickets in a Developing Country.

INTRODUCTION: X-linked hypophosphatemic rickets is part of a larger group of hereditary diseases characterized by renal phosphate loss, which causes growth disorders, rickets, and osteomalacia. These conditions are characterized by disorders in phosphate equilibrium, which is essential for bone formation. CASE REPORT: A female patient presented with bone deformities of the inferior extremities, prominent joints, and loss of teeth. She received initial management with oral calcium and orthotics in inferior extremities, with poor clinical outcome. PHEX gene sequencing revealed a pathogenic variant c.1601C>T (p.Pro534Leu). DISCUSSION: XLHR is caused by mutations in the PHEX gene; to date, more than 460 mutations have been associated with the disease. Clinically, it is characterized by bowing of the lower extremities, decreased growth, musculoskeletal complaints, dental abscesses, and other clinical signs and symptoms of rickets.