Global Developmental Delay in a Mexican Patient With Megalencephalic Leukoencephalopathy With Subcortical Cysts

Introduction: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a neurologic disorder characterized by macrocephaly within the first year of life and the delayed onset of motor function deterioration with ataxia and spasticity. Magnetic resonance imaging of the brain is diagnostic and shows diffusely abnormal, mildly swollen cerebral white matter and subcortical cysts. MLC exhibits an autosomal recessive mode of inheritance. Two genes have been associated with MLC. The first and most important gene is MLC1, The other gene involved is HEPACAM. Case Presentation: We studied a Mexican patient with a compatible diagnosis of MLC. The patient exhibited the c.353C > T, p.Thr118Met mutation, and both parents were carriers for the same mutation. To the best of our knowledge, no other cases of MLC have been reported in Mexican patient. This patient exhibited rapid deterioration of motor function. Conclusions: A diagnosis of MLC, which can be facilitated by imaging studies, should be considered in all patients who exhibit global developmental delay

Global Developmental Delay in a Mexican Patient With Megalencephalic Leukoencephalopathy With Subcortical Cysts

Introduction: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a neurologic disorder characterized by macrocephaly within the first year of life and the delayed onset of motor function deterioration with ataxia and spasticity. Magnetic resonance imaging of the brain is diagnostic and shows diffusely abnormal, mildly swollen cerebral white matter and subcortical cysts. MLC exhibits an autosomal recessive mode of inheritance. Two genes have been associated with MLC. The first and most important gene is MLC1, The other gene involved is HEPACAM. Case Presentation: We studied a Mexican patient with a compatible diagnosis of MLC. The patient exhibited the c.353C > T, p.Thr118Met mutation, and both parents were carriers for the same mutation. To the best of our knowledge, no other cases of MLC have been reported in Mexican patient. This patient exhibited rapid deterioration of motor function. Conclusions: A diagnosis of MLC, which can be facilitated by imaging studies, should be considered in all patients who exhibit global developmental delay

Unique spectrum of GJB2 mutations in Mexico

The aim of this study was to elucidate the involvement of mutations in three relatively common deafness genes in Mexican individuals with non-syndromic hearing loss. We sequenced GJB2 for mutations, screened for two deletions involving GJB6, del(GJB6-D13S1830) and del(GJB6-D13S1854), and for the m.1555A>G mutation in the MTRNR1 gene in 76 (71 simplex and 5 multiplex) unrelated Mexican probands with prelingual non-syndromic hearing loss. Samples were obtained from the Department of Genetics at Instituto Nacional de Rehabilitacion in Mexico City. Eight previously reported pathogenic variants and two polymorphic variants in GJB2 were identified. The two screened GJB6 deletions and the m.1555A>G mutation were not detected. Eight cases (10.6%) were found to have bi-allelic mutations in GJB2 and six (7.9%) were found to have a monoallelic GJB2 mutation. Of the six monoallelic mutations, one (p.R184Q) was a previously reported autosomal dominant variant. The most frequent pathological allele detected in this population was the c.35delG mutation in the GJB2 gene. The p.V27I polymorphic variant was also detected, with an allele frequency of 0.24. All eight probands with GJB2 mutations had symmetric profound deafness, whereas patients without GJB2 mutations had moderate, severe or profound hearing loss. This study shows that GJB2 mutations are an important cause of prelingual deafness in the Mexican population

Novel pathogenic variants underlie SLC26A4-related hearing loss in a multiethnic cohort

WOS: 000413713100030PubMed ID: 28964290Objectives: The genetics of sensorineural hearing loss is characterized by a high degree of heterogeneity. Despite this heterogeneity, DNA variants found within SLC26A4 have been reported to be the second most common contributor after those of GJB2 in many populations. Methods: Whole exome sequencing and/or Sanger sequencing of SLC26A4 in 117 individuals with sensorineural hearing loss with or without inner ear anomalies but not with goiter from Turkey, Iran, and Mexico were performed. Results: We identified 27 unique SLC26A4 variants in 31 probands. The variants c.1673A > G (p.N558S), c.1708-1G > A, c.1952C > T (p.P651L), and c.2090-1G > A have not been previously reported. The p.N558S variant was detected in two unrelated Mexican families. Conclusion: A range of SLC26A4 variants without a common recurrent mutation underlies SLC26A4-related hearing loss in Turkey, Iran, and Mexico. (C) 2017 Elsevier B.V. All rights reserved.National Institutes of Health grantsUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01DC009645, R01DC012836]This work was supported by National Institutes of Health grants R01DC009645 and R01DC012836 to M.T

Comprehensive Analysis Via Exome Sequencing Uncovers Genetic Etiology In Autosomal Recessive Non-Syndromic Deafness In A Large Multiethnic Cohort

Purpose Autosomal recessive non-syndromic deafness (ARNSD) is characterized by a high degree of genetic heterogeneity with reported mutations in 58 different genes. This study was designed to detect deafness causing variants in a multiethnic cohort with ARNSD by using whole-exome sequencing (WES). Methods After excluding mutations in the most common gene, GJB2, we performed WES in 160 multiplex families with ARNSD from Turkey, Iran, Mexico, Ecuador and Puerto Rico to screen for mutations in all known ARNSD genes. Results We detected ARNSD-causing variants in 90 (56%) families, 54% of which had not been previously reported. Identified mutations were located in 31 known ARNSD genes. The most common genes with mutations were MYO15A (13%), MYO7A (11%), SLC26A4 (10%), TMPRSS3 (9%), TMC1 (8%), ILDR1 (6%) and CDH23 (4%). Nine mutations were detected in multiple families with shared haplotypes suggesting founder effects. Conclusion We report on a large multiethnic cohort with ARNSD in which comprehensive analysis of all known ARNSD genes identifies causative DNA variants in 56% of the families. In the remaining families, WES allows us to search for causative variants in novel genes, thus improving our ability to explain the underlying etiology in more families.PubMedWoSScopu