Rare FMR1 gene mutations causing fragile X syndrome: A review

Autor: Merlin G. Butler, Adam F. Sitzmann, Robert Tanner Hagelstrom, Flora Tassone, Randi J Hagerman
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Autism
DNA Mutational Analysis
Fragile X Mental Retardation Protein
Congenital
Exon
FMR1 gene
Intellectual disability
2.1 Biological and endogenous factors
Missense mutation
fragile X syndrome
Aetiology
Child
Genetics (clinical)
Pediatric
Genetics
High-Throughput Nucleotide Sequencing
Exons
Fragile X syndrome
Phenotype
Mental Health
Mutation (genetic algorithm)
FMRP
congenital
hereditary
and neonatal diseases and abnormalities
Genotype
Intellectual and Developmental Disabilities (IDD)
Clinical Sciences
Nonsense mutation
Mutation
Missense
review
rare mutations
Article
03 medical and health sciences
Rare Diseases
Clinical Research
Behavioral and Social Science
medicine
Humans
Alleles
Genetic Association Studies
business.industry
Facies
medicine.disease
FMR1
Brain Disorders
nervous system diseases
Orphan Drug
030104 developmental biology
Fragile X Syndrome
Mutation
Missense
business
Zdroj: American journal of medical genetics. Part A, vol 176, iss 1
ISSN: 1552-4825
DOI: 10.1002/ajmg.a.38504
Popis: Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, typically due to CGG-repeat expansions in the FMR1 gene leading to lack of expression. We identified a rare FMR1 gene mutation (c.413G>A), previously reported in a single patient and reviewed the literature for other rare FMR1 mutations. Our patient at 10 years of age presented with the classical findings of FXS including intellectual disability, autism, craniofacial findings, hyperextensibility, fleshy hands, flat feet, unsteady gait, and seizures but without the typical CGG-repeat expansion. He had more features of FXS than the previously reported patient with the same mutation. Twenty individuals reported previously with rare missense or nonsense mutations or other coding disturbances of the FMR1 gene ranged in age from infancy to 50 years; most were verbal with limited speech, had autism and hyperactivity, and all had intellectual disability. Four of the 20 individuals had a mutation within exon 15, three within exon 5, and two within exon 2. The FMR1 missense mutation (c.413G>A) is the same as in a previously reported male where it was shown that there was preservation of the post-synaptic function of the fragile X mental retardation protein (FMRP), the encoded protein of the FMR1 gene was preserved. Both patients with this missense mutation had physical, cognitive, and behavioral features similarly seen in FXS.
Databáze: OpenAIRE
Externí odkaz: