The most common mutation, seen in >95% of Friedreich ataxia (FRDA) patients, is a GAA triplet-repeat expansion in intron 1 of the FXN gene. Individuals with less than 500 repeats often have a later age of onset compared to patients with greater than 600 repeats. The presence of leg muscle weakness/wasting, duration until wheelchair use, and prevalence of cardiomyopathy, pes cavus, and scoliosis also show statistically significant inverse correlations with the size of the expanded GAA repeat (PMID: 20301458). In some cases, the size of the repeat can even determine a patient’s eligibility for clinical trials. For these reasons, MNG Laboratories is proud to announce that we are now able to report the size of expanded alleles greater than 100 repeats detected by our FRDA repeat expansion testing.
If your patient has previously had abnormal FRDA testing performed by our lab, please contact us for free sizing.————————————————————————————————————————————————————-
MNG Laboratories is now offering deletion/duplication testing for congenital adrenal hyperplasia, Gaucher disease, alpha-thalassemia, and spinal muscular atrophy. Each of these disorders is caused by variations in genes that have highly homologous pseudogenes or other complex molecular characteristics that make deletion/duplication analysis by standard methods difficult. For that reason, we have validated Multiplex Ligation-dependent Probe Amplification (MLPA) testing for analysis of the genes associated with these disorders. Analysis of these genes will be included with all MNG Carrier Exomes™ and MNG Healthy Exomes™ at no additional cost to our clients. They are also available individually.
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that results from a deficiency in one of the enzymes involved in cortisol biosynthesis. CAH affects approximately 1 in 5,000 births, with an estimated carrier frequency of 1 in 35. In roughly 95% of cases, CAH is caused by deficiency of the steroid 21-hydroxylating enzyme encoded by the CYP21A2 gene (PMID: 20301350). Our CAH MLPA analysis will detect most large rearrangements/deletions/duplications within the CYP21A2 gene, as well as the presence of some of the most common pathogenic variants that are reported in the gene.
Gaucher disease (GD) is the most common lysosomal storage disorder, with a frequency as high as 1 in 850 in Ashkenazi Jewish populations (PMID: 24639522). GD is an autosomal recessive disorder characterized by a deficient activity/accumulation of beta-glucocerebrosidase. As a result of this deficiency, there is intracellular accumulation of glucosylceramide (GlcCer, glucosylcerebroside), primarily within cells of mononuclear phagocyte origin, which are the characteristic ‘Gaucher cells’ identified in most tissues. Defects in the GBA gene on chromosome 1q22 are the main cause of GD (PMID: 20301446). Our GD MLPA analysis will detect most large deletions/duplications within the GBA gene.
Alpha-thalassemia is the most common inherited hemoglobin disorder in the world. It is characterized by a reduced production of the alpha-globin chain, resulting in a decrease in the total amount of hemoglobin. The alpha-globin chains are encoded by the hemoglobin alpha 1 (HBA1) and alpha 2 (HBA2) genes, located in the alpha-globin gene cluster on chromosome 16p13.3. The associated patient phenotypes are dependent on which of the genes harbor pathogenic variants (HBA1 or HBA2), the type of variant, and the number of affected alpha-globin genes. Approximately 90% of alpha- thalassemia cases are attributed to deletions; more than 20 different deletions ranging from ~6 kb to >300 kb have been reported (20301608). Our alpha-thalassemia MLPA analysis will detect most large deletions/duplications within the HBA1 and HBA2 genes, as well as the Hb Constant Spring mutation (HbCS).
Spinal muscular atrophy (SMA) is an autosomal recessive condition characterized by muscle weakness and atrophy resulting from progressive degeneration and loss of the anterior horn cells in the spinal cord (i.e., lower motor neurons) and the brain stem nuclei. The onset of weakness ranges from before birth to adolescence or young adulthood. A homozygous deletion of exon 7 of the SMN1 gene is present in approximately 95% of SMA patients. Our SMA MLPA analysis will detect copy number of exons 7 and 8 of the SMN1 gene and of the SMN2 gene.