No abstract

Shawaf-Traboulsi syndrome (or Traboulsi syndrome; MIM 601552) is an infrequently reported entity characterized by a typical face (long face, large nose, convex nasal ridge, underdeveloped malae, crowded teeth, retrognathia), skeletal signs (long and slender fingers, sometimes pectus deformation and hypermobile joints), and ectopia lentis with conjunctival blebs, shallow anterior chamber and iridocorneal adhesions. The entity is caused by homozygous variants in ASPH. Here, we report on a boy with the clinical diagnosis of Shawaf-Traboulsi syndrome, in whom exome sequencing allowed identification of a novel variant in ASPH. We compare the findings in the present patient to those of earlier reported patients; furthermore add new signs for this entity.

Background We report the molecular analysis of the DMD gene in a group of Peruvian patients with Duchenne/Becker dystrophinopathy. This is the first study to thoroughly characterize mutations in this population. Methods We used the combination of multiplex ligation‐dependent probe amplification (MLPA) and sequencing analysis of the DMD gene. We recruited Peruvian patients in 2 years from reference national hospitals. We performed DNA tests in 152 patients, checking first exon deletion/duplication by MLPA, and subsequently, if negative, samples were sequenced to detect point mutations. Results The average age for diagnosis was 9.8 years, suggesting a delay for timely diagnosis and care. We found causal DMD mutations in 125 patients: 72 (57.6%) exon deletions/duplications (41.6% deletions, 16.0% duplications), and 53 (42.4%) point mutations (27.2% nonsense, 9.6% small indels, and 5.6% splice site). Conclusion Due to our genetic background, we expected a higher number of novel and recurrent causal mutations in our sample. Results showed 16% of novel mutations, similar to other well‐studied populations.

Pathogenic variants of the <i>GATAD2B</i> gene (1q21.3) are linked to intellectual disability autosomal dominant type 18 (MRD18; MIM 615074), characterized by dysmorphic features, psychomotor and language delay. We present an 11-year-old female patient with intellectual disability and typical clinical characteristics of MRD18. Chromosomal microarray analysis (CMA) revealed a novel CNV, approximately 200 kb in size and showed that the <i>INTS3</i> and <i>SLC27A3</i> genes are completely deleted along with the first 10 exons of the <i>GATAD2B</i> gene. <i>INTS3 </i>encodes the integrator complex subunit 3 and is part of the complex that maintains genome stability; <i>SLC27A3</i> encodes a fatty acid transporter and has been associated with autism spectrum disorder. <i>GATAD2B </i>haploinsufficiency is associated with the phenotype. Furthermore, the girl had other clinical characteristics not previously described, such as emotional instability, calf hypotrophy, hypoplastic digit pads, tapered thumbs, and anterior earlobe crease. This study highlights the importance of the phenotype-genotype correlation using molecular diagnostic techniques, such as CMA, and its impact on precise diagnosis, treatment, prognosis, and genetic counseling for patients and their families.

Las distonías que responden a levodopa (DRD, siglas en inglés) abarcan un grupo de distonías primarias, causadas por deficiencias enzimáticas en la vía metabólica de las aminas y, por definición, comparten como característica principal su respuesta favorable y sostenida a levodopa. Existen hasta seis genes asociados a DRD, siendo el gen GCH1 el más frecuentemente involucrado. La presentación típica de esta entidad se caracteriza por su aparición en la niñez, distonía de inicio en miembros inferiores con fluctuación diurna, leve parkinsonismo y respuesta clara a dosis bajas de levodopa. Se incluye una búsqueda sistemática de la literatura con casos de DRD publicados en Latinoamérica.