Sequencing of candidate genes selected by beta cell experts in monogenic diabetes of unknown aetiology.
BACKGROUND
Approximately 39% of cases with permanent neonatal diabetes (PNDM) and about 11% with maturity onset diabetes of the young (MODY) have an unknown genetic aetiology. Many of the known genes causing MODY and PNDM were identified as being critical for beta cell function before their identification as a cause of monogenic diabetes.


OBJECTIVE
We used nominations from the EU beta cell consortium EURODIA project partners to guide gene candidacy.


METHODS
Seventeen cases with permanent neonatal diabetes and 8 cases with maturity onset diabetes of the young.


METHODS
The beta cell experts within the EURODIA consortium were asked to nominate 3 "gold", 3 "silver" and 4 "bronze" genes based on biological or genetic grounds. We sequenced twelve candidate genes from the list based on evidence for candidacy.


RESULTS
Sequencing ISL1, LMX1A, MAFA, NGN3, NKX2.2, NKX6.1, PAX4, PAX6, SOX2, SREBF1, SYT9 and UCP2 did not identify any pathogenic mutations.


CONCLUSIONS
Further work is needed to identify novel causes of permanent neonatal diabetes and maturity onset diabetes of the young utilising genetic approaches as well as further candidate genes.
Edghill
Emma L
EL
Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom.
Minton
Jayne A L
JA
Groves
Christopher J
CJ
Flanagan
Sarah E
SE
Patch
Ann-Marie
AM
Rubio-Cabezas
Oscar
O
Shepherd
Maggie
M
Lenzen
Sigurd
S
McCarthy
Mark I
MI
Ellard
Sian
S
Hattersley
Andrew T
AT
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003920:Diabetes Mellitus / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D005104:Expert Testimony; D005260:Female; D005787:Gene Frequency; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014157:Transcription Factors; D055815:Young Adult