Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous p.R1419H ABCC8 mutation: an unusual clinical picture

2015 ◽  
Vol 0 (0) ◽  
Author(s):  
Shira Harel ◽  
Ana S.A. Cohen ◽  
Khalid Hussain ◽  
Sarah E. Flanagan ◽  
Kamilla Schlade-Bartusiak ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Insulin Secretion ◽  
Patch Clamp ◽  
Sanger Sequencing ◽  
Postprandial Hyperglycemia ◽  
Loss Of Function ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Rubidium Efflux ◽  
Expression And Activity

AbstractInheritance of two pathogenicSingle nucleotide polymorphism microarray and Sanger sequencing were performed. Western blot, rubidium efflux, and patch clamp recordings interrogated the expression and activity of the mutant protein.A 16-month-old girl of consanguineous descent manifested hypoglycemia. She had dysregulation of insulin secretion, with postprandial hyperglycemia followed by hypoglycemia. Microarray revealed homozygosity for the regions encompassingThis is the first description of a homozygous p.R1419H mutation. Our findings highlight that homozygous loss-of-function mutations of

scholarly journals Dominant Distal Myopathy 3 (MPD3) Caused by a Deletion in the HNRNPA1 Gene

2021 ◽  
Vol 7 (6) ◽  
pp. e632
Author(s):  
Peter Hackman ◽  
Salla M. Rusanen ◽  
Mridul Johari ◽  
Anna Vihola ◽  
Per Harald Jonson ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Rna Sequencing ◽  
Genome Sequencing ◽  
Sanger Sequencing ◽  
Genetic Defect ◽  
Distal Myopathy ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Muscle Biopsies ◽  
Exon 10

Background and ObjectivesTo determine the genetic cause of the disease in the previously reported family with adult-onset autosomal dominant distal myopathy (myopathy, distal, 3; MPD3).MethodsContinued clinical evaluation including muscle MRI and muscle pathology. A linkage analysis with single nucleotide polymorphism arrays and genome sequencing were used to identify the genetic defect, which was verified by Sanger sequencing. RNA sequencing was used to investigate the transcriptional effects of the identified genetic defect.ResultsSmall hand muscles (intrinsic, thenar, and hypothenar) were first involved with spread to the lower legs and later proximal muscles. Dystrophic changes with rimmed vacuoles and cytoplasmic inclusions were observed in muscle biopsies at advanced stage. A single nucleotide polymorphism array confirmed the previous microsatellite-based linkage to 8p22-q11 and 12q13-q22. Genome sequencing of three affected family members combined with structural variant calling revealed a small heterozygous deletion of 160 base pairs spanning the second last exon 10 of the heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) gene, which is in the linked region on chromosome 12. Segregation of the mutation with the disease was confirmed by Sanger sequencing. RNA sequencing showed that the mutant allele produces a shorter mutant mRNA transcript compared with the wild-type allele. Immunofluorescence studies on muscle biopsies revealed small p62 and larger TDP-43 inclusions.DiscussionA small exon 10 deletion in the gene HNRNPA1 was identified as the cause of MPD3 in this family. The new HNRNPA1-related phenotype, upper limb presenting distal myopathy, was thus confirmed, and the family displays the complexities of gene identification.

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