RESUMEN
MYH7-related disease (MRD) is the most common hereditary primary cardiomyopathy (CM), with pathogenic MYH7 variants accounting for approximately 40% of familial hypertrophic CMs. MRDs may also present as skeletal myopathies, with or without CM. Since pathogenic MYH7 variants result in highly variable clinical phenotypes, from mild to fatal forms of cardiac and skeletal myopathies, genotype-phenotype correlations are not always apparent, and translation of the genetic findings to clinical practice can be complicated. Data on genotype-phenotype correlations can help facilitate more specific and personalized decisions on treatment strategies, surveillance, and genetic counseling. We present a series of six MRD pedigrees with rare genotypes, encompassing various clinical presentations and inheritance patterns. This study provides new insights into the spectrum of MRD that is directly translatable to clinical practice.
Asunto(s)
Miosinas Cardíacas/genética , Cardiomiopatías/diagnóstico , Cardiomiopatías/genética , Estudios de Asociación Genética , Genotipo , Mutación , Cadenas Pesadas de Miosina/genética , Fenotipo , Adulto , Variación Biológica Poblacional , Biopsia , Niño , Preescolar , Análisis Mutacional de ADN , Ecocardiografía , Humanos , Lactante , Patrón de Herencia , Cariotipificación , LinajeRESUMEN
The term isolated ectopia lentis (EL; subluxation or dislocation of the human crystalline lens) is applied to patients with EL, without skeletal features and in the absence of aortic root dilatation. To date, the only gene shown to cause autosomal-recessive isolated EL is ADAMTSL4. Here we report a novel founder mutation in ADAMTSL4 gene in children of Bukharian Jewish origin presenting with early-onset bilateral EL. A carrier frequency of 1:48 was determined among unrelated healthy Bukharian Jews. Given the complications associated with disease and the allele frequency, a population screening for individuals of this ancestry is warranted in order to allow prenatal, pre-implantation or early postnatal diagnosis.
Asunto(s)
Desplazamiento del Cristalino/etnología , Desplazamiento del Cristalino/genética , Heterocigoto , Judíos , Cristalino/patología , Mutación Missense , Trombospondinas/genética , Proteínas ADAMTS , Preescolar , Desplazamiento del Cristalino/patología , Femenino , Efecto Fundador , Frecuencia de los Genes , Genotipo , Homocigoto , Humanos , Lactante , Masculino , Linaje , Adulto JovenRESUMEN
Renal coloboma syndrome, also known as papillorenal syndrome is an autosomal-dominant disorder characterized by ocular and renal malformations. Mutations in the paired-box gene, PAX2, have been identified in approximately half of individuals with classic findings of renal hypoplasia/dysplasia and abnormalities of the optic nerve. Prior to 2011, there was no actively maintained locus-specific database (LSDB) cataloguing the extent of genetic variation in the PAX2 gene and phenotypic variation in individuals with renal coloboma syndrome. Review of published cases and the collective diagnostic experience of three laboratories in the United States, France, and New Zealand identified 55 unique mutations in 173 individuals from 86 families. The three clinical laboratories participating in this collaboration contributed 28 novel variations in 68 individuals in 33 families, which represent a 50% increase in the number of variations, patients, and families published in the medical literature. An LSDB was created using the Leiden Open Variation Database platform: www.lovd.nl/PAX2. The most common findings reported in this series were abnormal renal structure or function (92% of individuals), ophthalmological abnormalities (77% of individuals), and hearing loss (7% of individuals). Additional clinical findings and genetic counseling implications are discussed.