J Korean Med Sci.  2012 May;27(5):565-568. 10.3346/jkms.2012.27.5.565.

Two Novel Insulin Receptor Gene Mutations in a Patient with Rabson-Mendenhall Syndrome: The First Korean Case Confirmed by Biochemical, and Molecular Evidence

• Kim D
• Cho SY
• Yeau SH
• Park SW
• Sohn YB
• Kwon MJ
• Kim JY
• Ki CS
• Jin DK

• KMID: 1372803
• DOI: http://doi.org/10.3346/jkms.2012.27.5.565

Abstract

Rabson-Mendenhall syndrome (RMS) is a rare syndrome manifested by extreme insulin resistance with hyperinsulinemia, acanthosis nigricans, tooth dysplasia and growth retardation. Our patient was first noted at the age of 8 months due to pigmentations on skin-folded areas. Initial laboratory tests showed normal fasting glucose (69 mg/dL). Fasting insulin level was severely elevated, up to 554.6 microIU/mL, and c-peptide level was increased, up to 13.81 ng/mL. However, hemoglobin A1c was within normal range (4.8%). He is now 11 yr old. His growth development followed the 5-10th percentile and oral hypoglycemic agents are being administered. The last laboratory results showed insulin 364.1 microIU/mL, C-peptide 4.30 ng/mL, and hemoglobin A1c 7.6%. The boy was a compound heterozygote for the c.90C > A and c.712G > A mutations of the insulin receptor gene, INSR, which are nonsense and missense mutations. In summary, we report the first Korean case of RMS, which was confirmed by two novel mutations of the INSR.

Keyword

Rabson-Mendenhall Syndrome; Insulin Resistance; Receptor, Insulin; INSR

MeSH Terms

Asian Continental Ancestry Group/*genetics
Base Sequence
Blood Glucose/analysis
C-Peptide/blood
Codon, Nonsense
Donohue Syndrome/drug therapy/*genetics
Heterozygote
Humans
Hypoglycemic Agents/therapeutic use
Infant
Insulin/blood
Male
Mutation, Missense
Receptor, Insulin/*genetics
Republic of Korea
Sequence Analysis, DNA

Figure

• 

  Fig. 1 Dentition photographs were taken at the age of 10 yr old. Note the abnormal dentition, which includes proclined upper and lower incisors (A), and crowding on lower teeth, macrodontia (B).

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  Fig. 2 Direct sequencing of the INSR gene in our patient. Compound heterozygous for two mutations were identified: c.90C>A (p.Tyr30X) in exon 1 and c.712G>A (p.Glu238Lys) in exon 3 (arrows).

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