A novel ASPH variant extends the phenotype of Shawaf-Traboulsi syndrome.

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.

MLPA followed by target-NGS to detect mutations in the dystrophin gene of Peruvian patients suspected of DMD/DMB.

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.

GATAD2B Gene Microdeletion Causing Intellectual Disability Autosomal Dominant Type 18: Case Report and Review of the Literature.

Pathogenic variants of the GATAD2B 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 INTS3 and SLC27A3 genes are completely deleted along with the first 10 exons of the GATAD2B gene. INTS3 encodes the integrator complex subunit 3 and is part of the complex that maintains genome stability; SLC27A3 encodes a fatty acid transporter and has been associated with autism spectrum disorder. GATAD2B 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.

Novel contiguous gene deletion in peruvian girl with Trichothiodystrophy type 4 and glutaric aciduria type 3.

Trichothiodystrophy type 4 is a rare autosomal recessive and ectodermal disorder, characterized by dry, brittle, sparse and sulfur-deficient hair and other features like intellectual disability, ichthyotic skin and short stature, caused by a homozygous mutation in MPLKIP gene. Glutaric aciduria type 3 is caused by a homozygous mutation in SUGCT gene with no distinctive phenotype. Both genes are localized on chromosome 7 (7p14). We report an 8-year-old female with short stature, microcephaly, development delay, intellectual disability and hair characterized for dark, short, coarse, sparse and brittle associated to classical trichorrhexis microscopy pattern. Chromosome microarray analysis showed a 125 kb homozygous pathogenic deletion, which includes genes MPLKIP and SUGCT, not described before. This is the first case described in Peru of a novel contiguous gene deletion of Trichothiodystrophy type 4 and Glutaric aciduria type 3 performed by chromosome microarray analysis, highlighting the contribution and importance of molecular technologies on diagnosis of rare genetic conditions.

[Nutritional and functional state of patients with chronic obstructive pulmonary disease: effects of oral nutritional supplementation (OFOS study)]. / Estado nutricional y funcional en pacientes con enfermedad pulmonar obstructiva crónica: efectos de la suplementación nutricional oral (estudio OFOS).

INTRODUCTION: Weight loss and malnutrition are associated with a worse prognosis of chronic obstructive pulmonary disease (COPD). OBJECTIVE: The main objective of the OFOS study was to assess the efficacy and tolerability of a new nutritional oral formula in adults with COPD with weight loss or malnutrition. METHODS: Prospective, single-centre, randomized, open-label and controlled trial conducted in Lima (Peru). A total of 99 outpatients of both sexes were included (control [GC]: 49; supplement [GS]: 50), aged from 18 to 80 years old, who had been diagnosed with COPD and that suffered from malnutrition or involuntary weight loss during the last months. Nutritional, functional and quality of life (QoL) variables were evaluated during a three-month intervention. RESULTS: At three months, there was an increase of body mass index (BMI) and fat free mass index (FFMI) significantly higher in the GS: IMC 5.3% vs 2.9%, p < 0.001; FFMI 3.2% vs 1.9%, p = 0.019. The GS showed a reduction of cases with BMI < 21 kg/m2 equivalent to 69% vs33% in the GC (p = 0.004). Functional variables showed a favourable improvement trend in GS, being significant for the hand-grip test in the subgroup of patients with low FFMI (p = 0.001). All QoL studied variables significantly improved in both groups (p < 0.001). CONCLUSIONS: Oral supplementation with a complete, polymeric and normocaloric new nutritional formula for three months was well tolerated and effective for the nutritional support of patients diagnosed with COPD with weight loss or malnutrition.

INTRODUCCIÓN: la pérdida de peso y la desnutrición se asocian a un peor pronóstico de la enfermedad pulmonar obstructiva crónica (EPOC).OBJETIVO: el objetivo del estudio OFOS fue valorar la eficacia y tolerabilidad de una nueva fórmula nutricional oral en adultos con EPOC con pérdida de peso o desnutrición. MÉTODOS: estudio prospectivo, unicéntrico, aleatorizado, abierto y controlado realizado en Lima (Perú). Se incluyeron 99 pacientes ambulatorios de ambos sexos (control [GC]: 49; suplemento [GS]: 50), entre 18 y 80 años con diagnóstico de EPOC y con pérdida involuntaria de peso en los últimos meses o desnutrición. Se evaluaron variables nutricionales, funcionales y de calidad de vida (CV) durante un periodo de intervención de tres meses. RESULTADOS: a los tres meses, hubo un incremento del índice de masa corporal (IMC) y del índice de masa libre de grasa (IMLG) significativamente superior en el GS: IMC: 5,3% vs.2,9%, p < 0,001; IMLG: 3,2% vs.1,9%, p = 0,019. El GS mostró una reducción de casos con IMC < 21 kg/m2 equivalente al 69% vs.33% en el GC (p = 0,004). Las variables funcionales mostraron una tendencia a la mejoría favorable al GS, siendo significativa para la fuerza de la mano (hand-grip test)en el subgrupo de pacientes con IMLG bajo (p = 0,001). Todas las variables estudiadas de CV mejoraron significativamente en ambos grupos (p < 0,001). CONCLUSIONES: la suplementación oral durante tres meses con una nueva fórmula completa, polimérica y normocalórica fue bien tolerada y eficaz para el soporte nutricional de pacientes diagnosticados de EPOC con pérdida de peso o desnutrición.

Genetic studies to determine the risk of non-ischemic sudden death: review article / Estudios genéticos para determinar el riesgo de muerte súbita no isquémica: artículo de revisión

Heart disease is the cause of sudden death in more than 80% of cases. Ischemic heart disease is the cause for 90% of all sudden cardiac deaths, while in the remaining 10% of cases, heart diseases have a hereditary origin and comprise a wide spectrum of disorders that include cardiomyopathies and channelopathies. The aim of this review is to highlight the importance of genetic counseling for patients with hereditary cardiovascular disease and its evaluation by a multidisciplinary team.

La cardiopatía es la causa de muerte súbita en más del 80% de casos. La cardiopatía isquémica es responsable en el 90% del total de las muertes súbitas cardiacas, mientras que en el 10% de casos restantes, las cardiopatías tienen un origen hereditario y comprenden un amplio espectro de trastornos que incluyen a las cardiomiopatías y las canalopatías. El objetivo de esta revisión es poner en evidencia la importancia del asesoramiento genético de los pacientes con enfermedad cardiovascular hereditaria y su evaluación a través de un equipo multidisciplinario.

Variantes en el número de copias en trastornos del neurodesarrollo, síndrome malformativo y talla baja en Perú / Copy number variation in development disorders, malformative syndrome and short stature in Peru

RESUMEN Objetivo : determinar las variantes en el número de copias y regiones de homocigosidad mediante el análisis cromosómico por micromatrices, en niños con diagnóstico de trastorno del neurodesarrollo: retraso del desarrollo psicomotor (RDPM), discapacidad intelectual (DI) y trastorno del espectro autista (TEA), así como pacientes con síndrome malformativo (SM) y talla baja idiopática (TBI). Materiales y métodos : se evaluaron a 367 niños peruanos diagnosticados clínicamente con DI, RDPM, TEA, TBI y SM a quienes se les realizó el análisis cromosómico por micromatrices (CMA 750K CGH+SNP) en sangre periférica, entre los años 2016-2018. Resultados : las edades fluctuaron entre los 4,8 meses y los 18 años, con una media de 5,6 años. Los diagnósticos más frecuentes fueron RDPM (48%) y DI (30%). Se reportaron resultados anormales (variantes patogénicas, probablemente patogénicas, disomías uniparentales y regiones de homocigosidad superiores a 2,56%) en el 50,3% de los pacientes. Los resultados anormales se observaron en el 53,3% de los casos con diagnóstico de DI y el 47,9% de RDPM; mientras que en el resto de los casos con TBI sindrómica, SM y TEA tuvieron resultados anormales en el 52,4%, 52% y 20% respectivamente. Por otro lado, encontramos hasta un 6,2% de los padres eran consanguíneos no declarados. Conclusiones : la tasa de detección de las variantes en el número de copias (CNVs) encontrada en nuestro estudio fue superior a la reportada en estudios internacionales independientemente del diagnóstico clínico. Además, se pudo encontrar una mayor frecuencia de consanguinidad no declarada con relación a estudios anteriores.

ABSTRACT Objective: To establish the ratios of the copy number variations and regions of homozygosity through chromosomal microarray analysis (CMA) in children with neurodevelopmental disorders: development delay (DD), intellectual disability (ID), and/or autistic spectrum disorder (ASD), malformative syndrome (MS) and idiopathic short stature (ISS). Materials and Methods: We evaluated 367 Peruvian children diagnosed clinically with ID, DD, ASD, ISS and MS to whom performed chromosomal microarray analysis in peripheral blood (750K CGH + SNP), between the years 2016-2018. Results: Patients' age fluctuated between 4.8 months and 18 years old, with an average of 5.6 years old. The most frequent diagnoses were development delay (48%) and intellectual disability (30%). Abnormal results (pathogenic variants, likely pathogenic variants, uniparental disomies and loss of heterozygosity> 2.5%) were reported in 50.3%. The 53.28% of the cases with a diagnosis of intellectual disability and 47.92% of development delay showed abnormal results; while the children with short stature syndromic, malformative syndrome, and autistic disorders spectrum disorders showed abnormal results in 52.38%, 52% and 20% respectively. Additionally, we found that 6.25% of parents were non-declared consanguinity. Conclusions: Abnormal results found in our study was a higher ratio than other international reports regardless of the clinical diagnosis. Furthermore, we show a most rate of non-declared consanguinity in relation with previous reports.

Síndrome de Pfeiffer tipo 2: diagnóstico prenatal. Reporte de caso y revisión de la literatura / Pfeiffer Syndrome Type 2: Prenatal diagnosis. Case report and literature review

Pfeiffer syndrome is an autosomic dominant disorder characterized by craniosynostosis, midface hypoplasia and syndactyly of the hands and feet. Three different phenotypes have been described, where type 2 is the most severe and the one amenable of prenatal diagnosis. We present the first clinical case reported at Instituto Nacional Materno Perinatal, Lima, Peru, of a fetus with suspicious ultrasound prenatal findings of this syndrome including cloverleaf-shaped skull, severe ventriculomegaly, frontal bossing, ocular proptosis and overlapped fingers, who was born by cesarean section and died at day eight due to progressive respiratory distress.

El síndrome de Pfeiffer es una enfermedad rara de tipo autosómica dominante caracterizada por craneosinostosis bicoronal, hipoplasia medio facial y sindactilia de manos y pies. Se ha descrito 3 fenotipos, siendo el tipo 2 el más severo y que generalmente se diagnostica prenatalmente. Presentamos el primer caso descrito en el Instituto Nacional Materno Perinatal de Lima, Perú, de un feto con hallazgos ultrasonográficos sospechosos de este síndrome, como el cráneo en forma de trébol, ventriculomegalia severa, frente abombada, ojos protruidos y dedos superpuestos, que nació por cesárea y falleció a los 8 días de edad por distrés respiratorio progresivo.

Factores de riesgo en las enfermedades genéticas / Risk factors in genetic diseases

Existen más de 10 000 enfermedades genéticas descritas en el mundo y afectan alrededor del 7% de la población mundial, causando alta morbimortalidad y costos para los sistemas de salud pública. Representan un reto diagnóstico por la variabilidad clínica y la necesidad de pruebas diagnósticas moleculares. En el Perú, son escasas las investigaciones respecto a estas condiciones y, aunque se ha promulgado la Ley de Enfermedades Huérfanas o Raras (Ley Nº 29698), no se han implementado estrategias sanitarias nacionales para el diagnóstico, manejo y prevención. La presente publicación tiene como objetivo describir los factores de riesgo más frecuentes, los cuales están relacionados a enfermedades o síndromes de etiología genética

More than 10,000 genetic diseases have been described, which affect approximately 7% of the whole world population, leading to high morbidity and mortality rates, as well as to elevated healthcare costs. The diagnosis of these conditions is a tough challenge, because of their clinical variability and the low availability of molecular diagnostic tests. There is little research performed in Peru dealing with these diseases, and although a 'Bill for Orphan or Rare Diseases' (Law N° 29698) has been recently issued, no national healthcare strategies have been implemented for the diagnosis, management, and prevention of genetic diseases. This paper aims to describe the risk factors that are more frequently related to diseases or syndromes with a genetic origin