Facing the challenges to shorten the diagnostic odyssey: first Whole Genome Sequencing experience of a Colombian cohort with suspected rare diseases.

Exome and genome sequencing (ES/GS) are routinely used for the diagnosis of genetic diseases in developed countries. However, their implementation is limited in countries from Latin America. We aimed to describe the results of GS in patients with suspected rare genetic diseases in Colombia.

Novel progressive acrodysostosis-like skeletal dysplasia, cerebellar atrophy, and ichthyosis.

Acrodysostosis refers to a rare heterogeneous group of bone dysplasias that share skeletal features, hormone resistance, and intellectual disability. Two genes have been associated with acrodysostosis with or without hormone resistance (PRKAR1A and PDE4D). Severe intellectual disability has been reported with acrodysostosis but brain malformations and ichthyosis have not been reported in these syndromes.

Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA.

Background: As mucopolysaccharidosis IVA (MPS IVA) is the most frequent MPS in Colombia, this paper aims to describe its clinical and mutational characteristics in 32 diagnosed patients included in this study.

Methods: Genotyping was completed by amplification and Sanger sequencing of the GALNS gene. The SWISS-model platform was used for bioinformatic analysis, and mutant proteins were generated by homology from the wild-type GALNS code 4FDI template from the Protein Data Bank (PDB) database.

Novel mutation of FKBP10 in a pediatric patient with osteogenesis imperfecta type XI identified by clinical exome sequencing.

Osteogenesis imperfecta (OI) is a hereditary disease characterized by bone fragility caused by mutations in the proteins that support the formation of the extracellular matrix in the bone. The diagnosis of OI begins with clinical suspicion, from phenotypic findings at birth, low-impact fractures during childhood or family history that may lead to it. However, the variability in the semiology of the disease does not allow establishing an early diagnosis in all cases, and unfortunately, specific clinical data provided by the literature only report 28 patients with OI type XI.

[Characterization of patients with skeletal genetic diseases in a Colombian referral center].

Introduction: Short height in Colombia has an estimated prevalence of 10%. The 2009 Nosology and Classification of Skeletal Genetic Diseases described 456 clinical conditions using biochemical, molecular and radiological criteria for diagnosis.

Objective: To analyze demographic, epidemiological and clinical variables in a group of patients with skeletal genetic diseases referred to the Instituto de Ortopedia Infantil Roosevelt.

[Clinical community genetics: exploring genetic disorders in Boyacá, Colombia].

Objectives: To explore the incidence of syndromic genetic pathologies in Boyacá, Colombia, through a community genetics approach.

Materials And Methods: A group made up by different medical specialists (geneticists, a pediatric neurologist, and a biochemical geneticist) developed clinical campaigns, in which patients with clinical suspicion of genetic diseases were involved. Demographic, epidemiological and clinical data were collected, and frequency calculations were made based on the collected data.

Natural History of Sanfilippo Syndrome Type C in Boyacá, Colombia.

Mucopolysaccharidosis type III, or Sanfilippo syndrome, is an autosomal recessive disorder characterized by impairment in the degradation of Heparan sulfate. Here the authors describe the natural history of 5 related individuals; all associated through a large pedigree which reports a total of 11 affected members, originally from the Boyacá region in Colombia, diagnosed with MPS IIIC who all harbor a novel mutation in HGSNAT. The authors report an unusually high incidence of the disease in this population.

Charcot Marie Tooth disease (CMT4A) due to GDAP1 mutation: report of a Colombian family.

Background: Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth disease and more than 40 different mutations have been reported. The recessive Q163X mutation has been described in patients of Spanish ancestry, and a founder mutation in South American patients, originating in Spain has been demonstrated.

Objective: We describe physical and histological features, and the molecular impact of mutation Q163X in a Colombian family.

Genotypic and bioinformatic evaluation of the alpha-l-iduronidase gene and protein in patients with mucopolysaccharidosis type I from Colombia, Ecuador and Peru.

Mucopolysaccharidosis type I (MPSI) is a rare autosomal recessive disorder caused by mutations in the gene encoding the lysosomal enzyme α-l-iduronidase (IDUA), which is instrumental in the hydrolysis of the glycosaminoglycans, dermatan and heparan sulfate. The accumulation of unhydrolyzed glycosaminoglycans leads to pathogenesis in multiple tissue types, especially those of skeletal, nervous, respiratory, cardiovascular, and gastrointestinal origin. Although molecular diagnostic tools for MPSI have been available since the identification and characterization of the IDUA gene in 1992, Colombia, Ecuador, and Peru have lacked such methodologies.

SHOX gene and conserved noncoding element deletions/duplications in Colombian patients with idiopathic short stature.

SHOX gene mutations or haploinsufficiency cause a wide range of phenotypes such as Leri Weill dyschondrosteosis (LWD), Turner syndrome, and disproportionate short stature (DSS). However, this gene has also been found to be mutated in cases of idiopathic short stature (ISS) with a 3-15% frequency. In this study, the multiplex ligation-dependent probe amplification (MLPA) technique was employed to determine the frequency of SHOX gene mutations and their conserved noncoding elements (CNE) in Colombian patients with ISS.