Medical genetics in Paraguay is still in its infancy, with many tests being sent out of the country given the lack of local availability, no genetic counselors, no accredited post-doctoral residency training program in genetics, and only one clinical geneticist serving a country of almost 7 million people.

Terminal osseous dysplasia with pigmentary defects (TODPD) is an X-linked dominant syndrome with distal limb anomalies, pigmentary skin defects, digital fibromas, and generalized bone involvement due to a recurrent mutation in the filamin A (FLNA) gene. We here report the mutation c.5217G>A in FLNA in three families with TODPD and we found possible germline and somatic mosaicism in two out of the three families.

We identified and characterized Brody myopathy in a family diagnosed with malignant hyperthermia (MH). Exome sequencing revealed compound heterozygous mutations in the SERCA1, a calcium pump, expressed in fast-twitch muscles. Analyses of affected muscles show the absence of SERCA1, but upregulation of SERCA2 demonstrating a compensatory mechanism that partially restores the diminished Ca²⁺ transport. MH diagnosis in the family is likely due to prolonged elevation of intracellular Ca²⁺.

Classic galactosemia results from deficiency in galactose-1-phosphate urydylyltransferase, GALT, a key enzyme in galactose metabolism. Herein, we show that the most frequent GALT mutations result in disturbed protein aggregation despite limited effects on secondary and tertiary structures. These observations shed new light on the molecular basis for pathogenicity in the most frequent GALT mutations, suggesting alternative therapeutic interventions for classic galactosemia.

Based on the largest number of skeletal dysplasia cases, this study provides valuable information on Fibroblast growth factor receptor 3 (FGFR3) mutation frequency of four skeletal dysplasias for clinical diagnostic laboratories and clinicians.

The objective of the present study was molecular analysis of ATM gene in a cohort of 24 Polish patients with ataxia-telangiectasia in aim to provide an updated mutational spectrum in Polish AT patients. As result of molecular analysis status of recurrent mutation was confirmed and also ten new ATM variants were detected.

Array comparative genomic hybridization identifies a 2p16.3 deletion that includes the NRXN1 gene in three unrelated patients who share the same dysmorphic, cognitive, and psychiatric phenotype. The exhaustive neuropsychological assessment of the family members who carry the deletion showed an intelligence quotient from borderline to average and all present an anxiety disorder and a dysexecutive syndrome. We suggest that the NRXN1 gene is a risk factor for intellectual disability and psychiatric disorder with variable expressivity.

In a testing cohort of 17,880 individuals, we report that duplications (dup) (56.7%) or deletions (del) (21.9%) in the PMP22 gene accounted for the majority of positive findings followed by mutations in the GJB1 (6.7%), MPZ (5.3%), and MFN2 (4.3%) genes.

We describe a unique bioinformatic analysis of whole-genome sequences from a family trio designed to identify imprinted gene mutations that are often overlooked by inheritance-based analyses. Application of this approach to whole-genome sequencing data from a family with an affected child for whom multiple lines of investigation were nonexplanatory identified a CDKN1C mutation, thereby providing a diagnosis of IMAGe syndrome for the proband.

Five Duchenne muscular dystrophy (DMD) patients with complex genomic rearrangements were investigated using a combination of MLPA/mRNA transcript analysis/custom array CGH and breakpoint sequence analysis to investigate the mechanisms for these rearrangements. We propose replication-based mechanisms for all five complex DMD rearrangements.