Inherited Insulin Resistance Syndromes (INSR) Sequencing

Background Information for Inherited Insulin Resistance Syndromes (INSR) Sequencing:
Characteristics:  Extreme insulin resistance is characterized by abnormal glucose homeostasis and hyperinsulinemia, leading eventually to ketoacidosis. Donohue syndrome (leprechaunism), Rabson-Mendenhall syndrome, and Type A insulin resistance are all caused by INSR gene mutations, although severity and survival varies greatly among syndromes. Symptoms may include intrauterine growth restriction, failure to thrive after birth, characteristic dysmorphic features, lack of subcutaneous fat, acanthosis nigricans, enlargement of genitalia in males and females, cystic ovaries and amenorrhea in females, premature and dysplastic dentition, and pineal hyperplasia.
Incidence: Unknown; rare.
Inheritance: Autosomal recessive (Donohue and Rabson-Mendenhall syndromes). Type A insulin resistance can be autosomal recessive or dominant.
Cause: Pathogenic INSR gene mutations.
Clinical Sensitivity: Predicted to be greater than 90 percent in individuals with a clinical diagnosis.
Methodology: Bidirectional sequencing of the entire coding region and intron/exon boundaries of the INSR gene.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations, deep intronic mutations, and large deletions/duplications will not be detected.  Mutations in genes other than INSR are not evaluated.

Counseling and informed consent are recommended for genetic testing.  Consent forms are available online at www.aruplab.com.