Pathogenic variants in WAC are uncommon causes of developmental delay and neurobehavioral phenotypes. The clinical features associated with WAC haploinsufficiency include recognizable dysmorphic facial features that were recently delineated as DeSanto-Shinawi syndrome (DESSH; OMIM 616708). Additional clinical features include hypotonia, hearing and vision abnormalities, gastrointestinal problems, and behavioral difficulties. Here, we report a case of a 4-year-old Colombian male patient with typical dysmorphic facial features, developmental delay, hyperactivity, and recurrent respiratory infections. His immune workup revealed hypogammaglobulinemia, and clinical exome sequencing revealed a novel intronic variant in WAC (c.1437+1G>A). To the best of our knowledge, this is the first case of DESSH in South America, underlining the accumulating evidence of the significant role of WAC haploinsufficiency in neurobehavioral phenotypes. Although this report suggested the potential involvement of WAC in immune regulation, additional reports are required to confirm our observations.

Case Description:We report the case of a one-year-old girl who was diagnosed with Wiedemann-Steiner Syndrome based on the identification of a novel de novo frameshift mutation in the KMT2A gene by whole exome sequencing and supported by her clinical features. Clinical Findings:KMT2A mutations cause Wiedemann-Steiner Syndrome, a very rare genetic disorder characterized by congenital hypertrichosis, short stature, intellectual disability, and distinct facial features. Treatment and Outcome:Whole exome sequencing identified a novel frameshift variant: c. 4177dupA (p.Ile1393Asnfs * 14) in KMT2A; this change generates an alteration of the specific binding to non-methylated CpG motifs of the DNA to the protein. The genotype and phenotype of the patient were compared with those of earlier reported patients in the literature. Clinical Relevance:In diseases with low frequency, it is necessary to establish a genotype-phenotype correlation that allows the establishment of therapeutic and follow-up goals. The phenotype comparation with other reported cases did not show differences attributable to sex or age among patients with Wiedemann-Steiner Syndrome. Whole exome sequencing allows identifying causality in conditions with high clinical and genetic heterogeneity like hypertrichosis.

Background: Achondrogenesis type IA (ACG1A) is a rare, lethal autosomal recessive chondrodysplasia affecting endochondral bone ossification and differentiation, causing intrauterine growth restriction, narrow thorax, and short limbs. Mutations in TRIP11, which encodes Golgi microtubule-binding protein 210 in the Golgi apparatus, alter protein transport in tissues. Case presentation: A 28-week gestation male fetus was diagnosed with ACG1A by clinical, radiological, histologic, and molecular findings. Results: Whole exome sequencing was performed on fetal DNA and parental blood. Two fetal heterozygous novel variants of TRIP11, c.2304_2307delTCAA (p.Asn768Lysfs*7) and c.2128_2129delAT (p.lle710Cysfs*19), were inherited from the mother and father, respectively. Both variants created a reading frameshift leading to a premature stop codon and loss of protein function. Conclusion: To our knowledge, this is the first Latin American report with clinical, radiographic, and molecular diagnosis of ACG1A. Clinical and molecular diagnosis in utero is essential for genotype–phenotype correlation and is useful for providing better genetic counseling.

Background: Prader–Willi-like syndrome (PWLS) is believed to be caused by a variety of disruptions in genetic pathways both inside and outside of the genetic region implicated in PWS. By definition, PWLS does not demonstrate mutations in the 15q11–q13 region itself. It is a rare disorder whose clinical hallmarks include hypotonia, obesity, short extremities and delayed development. This syndrome has been described in patients with 1p, 2p, 3p, 6q and 9q chromosome abnormalities and in cases with maternal uniparental disomy of chromosome 14 and fragile X syndrome. Case presentation: In the present report, we describe a 9-year-old Colombian patient who demonstrated features of PWS and was ultimately diagnosed with PWLS after genetic analysis revealed a 14.97 Mb deletion of 6q16.1–q21. Conclusions: This is the first reported case of PWLS in Colombia and represents one of the largest documented 6q21 deletions. Keywords: Prader–Willi-like syndrome, Prader–Willi-like phenotype, Prader–Willi syndrome (PWS), 6q16.1–q21 deletion, Pediatric Obesity

Background: CYP2C19 is a highly polymorphic gene that encodes an enzyme with the same name and whose function is associated with the metabolism of many important drugs, such as proton pump inhibitors (such as esomeprazole, which is used for the treatment of acid peptic disease). Genetic variants in CYP2C19 alter protein function and affect drug metabolism. This study aims to genotypically and phenotypically characterize the genetic variants in the CYP2C19 gene in 12 patients with acid peptic disorders and different therapeutic profiles to proton pump inhibitor (PPI) drugs. The patients were randomly selected from a controlled, randomized and blinded clinical pilot trial of 33 patients. We determined the presence and frequency of single nucleotide polymorphisms (SNPs) within exons 1– 5 and 9, the intron-exon junctions, and a fragment in the 3ʹ UTR region of the CYP2C19 gene using Sanger sequencing. Undescribed polymorphisms were analyzed by free online bioinformatics tools to evaluate the potential molecular effects of these genetic variants. Results: We identified nine polymorphisms, six of which had no reported functions. One of these genetic variants, with a functional impact, not yet reported (p.Arg132Trp) was predicted by bioinformatic tools as potentially pathogenic. This finding suggests that p.Arg132Trp could be related to poor metabolizers of drugs metabolized by CYP2C19. Conclusion: We identified the genotype spectrum of variants in CYP2C19. The genotype spectrum of variants in CYP2C19 could predict the treatment response and could support to evaluate clinical efficacy in patients treated with esomeprazole.

Introduction: Mutations in ABCC9 are associated with Cantú syndrome (CS), a very rare genetic disorder characterized by congenital hypertrichosis, acromegaloid facial appearance (AFA), cardiomegaly, and skeletal anomalies. Case report: We report an 8-year-old female patient with congenital generalized hypertrichosis and coarse facial appearance but without cardiovascular or skeletal compromise. Whole exome sequencing revealed a novel de novo heterozygous mutation in ABCC9. In addition, the genotype and phenotype of the patient were compared with those of the patients reported in the literature and with other related conditions that include AFA, hypertrichosis and AFA, and CS. Conclusion: This is the first report of a South-American patient with mutation in ABCC9. We propose that her phenotype is a part of a spectrum of features associated with congenital hypertrichosis and mutations in ABCC9, which differs from CS and related disorders. Whole exome sequencing enabled the identification of the causality of this disease characterized by high clinical and genetic heterogeneity.