Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Ridge (biology) wikipedia , lookup
Promoter (genetics) wikipedia , lookup
Community fingerprinting wikipedia , lookup
Genomic imprinting wikipedia , lookup
Molecular evolution wikipedia , lookup
Exome sequencing wikipedia , lookup
Gene regulatory network wikipedia , lookup
Point mutation wikipedia , lookup
Silencer (genetics) wikipedia , lookup
Genome evolution wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
M YO PAT I C F E AT U R E S A N D AT Y P I C A L H Y S TO PAT H O L O G I C A L C H A N G E S I N A PAT I E N T W I T H C . 1 1 8 9 9 _ 1 1 9 0 7 + 5 D E L I N T H E E X O M E 8 6 P L U S 5 N U C L E OT I D E S I N T H E A D J A C E N T I N T R O N I N C L U D I N G T H E D O N O R S I T E O F S P L I C I N G I N RY R 1 G E N E Garza Saúl, Mayén Dora, Ramírez Eva, Sosa David. Hospital Ángeles Lomas. [email protected] INTRODUCTION Centronuclear myopathies (CNM) are congenital muscle diseases characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, with multiple modes of inheritance and various genes involved, including MTM1, DNM2, BIN1 and RYR1 (Jungblut et al, 2014) Clinically, RYR1-related CNM is of intermediate severity with facial weakness, ophthalmoplegia, predominantly proximal muscle involvement but less bulbar respiratory impairment (Wilmshurst et al., 2010). Patients with RYR1-related CNM show a marked tendency to improve overtime, even following an initially severe presentation (Bohm et al., 2012). The present is an atypical clinical case with a non-characteristic hystophatological biopsy and a probable new mutation. c.6067C>T (p.Leu2023Phe) RYR1 gene c.11899_11907+5d el RYR1 gene c.6067C>T (p.Leu2023Phe) / c.11899_11907+5d el RYR1 gene Figure 2. Results of NGS, the mutations was confirmed by Sanger CASE REPORT A 5 year-old boy born from healthy parents attended at the Genetics Clinic with muscular weakness and motor impairment since six months of age. In the family history, a maternal first-degree aunt with Down syndrome, a maternal seconddegree aunt with muscular dystrophy and a paternal first-degree uncle of 40 years old who recently developed muscular weakness. At the physical examination showed prominent ears with retroauricular fissures, permanent opened mouth, thorax assimetry and scoliosis. Multiple studies were performed to discard Fragile X, spinal muscular atrophy and Pompe disease, MLPA for syndromes associated with motor impairment, all of them were normal as well as a karyotype and a microarray study. Muscular enzymes, electromyography and nerve conduction velocity test were normal. The first muscular biopsy showed a myopatic pattern and the second one distrophyc changes. Figure 1. At 18 months, he showed myophatic face, bilateral palpebral ptosis and permanent opened mouth. The neurologic examination suggested a myopaty pattern, so we decided to perform next generation sequencing (NextGeneDx®) of ACTA1, MYH7, RYR1, SEPN1 and TPM3 genes. No abnormalities were seen in all genes except RYR1. The patient is heterozigous for c.6067C>T (p.Leu2013Phe) and also for a deletion of c.11899_11907+5del, no yet described in the literature. Figure 3. At 18 moths and 5 years, he showed thorax assymetry and scoliosis. DISCUSSION The c.6067C>T is a variant of unknown significance probably benign, meanwhile the c.11899_11907+5del is probably patogenic, since it includes a deletion in the exome 86 plus 5 nucleotides in the adjacent intron including the donor site of splicing. We suggested to the parents the analysis of both changes on them in order to established if those are inherited or de novo and if they are localized in the same or different alleles.