Identification of a Novel Homozygous INSR Variant in a Patient with Rabson-Mendenhall Syndrome from the United Arab Emirates.
OBJECTIVE
This study aimed to identify, clinically and molecularly, the causality of Rabson-Mendenhall syndrome in an Emirati family. It is one of the monogenic syndromes of abnormal glucose homeostasis, which result from insulin receptor defects.


METHODS
A novel nonsynonymous variant in the INSR gene was uncovered by whole exome sequencing and confirmed using Sanger sequencing in the patient and his parents. Various in silico tools were utilized to analyze the functional consequences of the variant.


RESULTS
Results revealed a previously unreported INSR variant in the family: c.421C>T (p.Arg141Trp). Homozygosity for the variant was found in the patient, while both parents were heterozygous.


CONCLUSIONS
The nonsynonymous protein change hit a highly conserved arginine residue in the insulin-binding α-subunit of the receptor and was deemed 'functionally damaging' by a myriad of bioinformatics tools. This report is a step forward along the way of achieving a better molecular and clinical characterization of Rabson-Mendenhall syndrome.
Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
Fatma
F
Bastaki
Pratibha
P
Nair
Madiha
M
Mohamed
Manal Mustafa
MM
Khadora
Fatima
F
Saif
Nafisa
N
Tawfiq
Mahmoud Taleb
MT
Al-Ali
Abdul Rezzak
AR
Hamzeh
D000328:Adult; D019943:Amino Acid Substitution; D015703:Antigens, CD / Q000235:genetics*; D002675:Child, Preschool; D056731:Donohue Syndrome / Q000235:genetics*; D005190:Family; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D011972:Receptor, Insulin / Q000235:genetics*; D014479:United Arab Emirates
D015703:Antigens, CD; C435941:INSR protein, human; D011972:Receptor, Insulin