Testing for monogenic diabetes among children and adolescents with antibody‐negative clinically defined Type 1 diabetes

Abstract

The identification of patients with monogenic diabetes from children with clinically defined Type 1 diabetes may be helped by clinical criteria including the absence of pancreatic autoantibodies.

Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

“…This is consistent with a recent study on children and adolescents by Rubio-Cabezas where 9,9% tested negative for the same pancreatic autoantibodies (20) We find that, when investigated in a physiologic setting, residual beta-cell function was considerably improved in autoantibody-negative (GADA, ICA, IA-2A) children with T1 D compared with autoantibodypositive (GADA, ICA, IA-2A) T1 D one year after diagnosis (Fig. 1A,B).…”

Frameshift mutations in the insulin gene leading to prolonged molecule of insulin in two families with Maturity-Onset Diabetes of the Young

“…All of these reported mutations were localized in the coding regions of the INS gene [Boesgaard et al, 2010;Bonfanti et al, 2009;Edghill et al, 2008;Meur et al, 2010;Molven et al, 2008;Moritani et al, 2013;Rubio-Cabezas et al, 2009], whereas point mutations in the promoter region, translation initiation site, 3 0 -untranslanted region and 24-base pair deletion were only observed in a recessive configuration in neonatal diabetes cases [Garin et al, 2010]. In addition, Garin et al has described a heterozygous intronic mutation in a patient with PNDM [Garin et al, 2012].…”

INS-gene mutations: From genetics and beta cell biology to clinical disease

“…Specifically, substitutions of arginine with either leucine, histidine, or proline at C-A junction results in proinsulin processing defects that are accompanied by relatively asymptomatic hyperproinsulinemia (Gabbay et al, 1979; Steiner et al, 1990), borderline glucose intolerance (Gruppuso et al, 1984), or late-onset mild diabetes (Oohashi et al, 1993; Yano et al, 1992). In contrast, substitution of arginine with cysteine at either B-C junction or C-A junction causes severe early onset insulin-deficient diabetes (Colombo et al, 2008; Edghill et al, 2008; Rubio-Cabezas et al, 2009; Stoy et al, 2007). Direct side-by-side comparison indicates that while the leucine substitution R89L is efficiently secreted from the cells, the cysteine substitution R89C causes proinsulin misfolding and retention in the ER (Colombo et al, 2008).…”

“… Re: recessive; Dn: Dominant; 3-UTR: 3′-untranslated region; IR: insulin receptor; ER: endoplasmic reticulum; SP: signal peptide; Ref: References. a The nomenclature of the nucleotide changes is based on the INS gene coding sequence where nucleotide 1 represents translational start site. b The patients that are homozygote or compound heterozygote for those recessive INS gene mutations develop diabetes in 6 mo after birth. c Few patients carrying those mutations develop diabetes after 6 mo. d Hyperproinsulinemia, borderline glucose intolerance, or late-onset mild diabetes. References: 1 (Garin et al, 2010); 2 (Raile et al, 2011); 3 (Hussain et al, 2013); 4 (Boesgaard et al, 2010); 5 (Meur et al, 2010); 6 (Edghill et al, 2008); 7 (Stoy et al, 2007); 8 (Polak et al, 2008); 9 (Colombo et al, 2008); 10 (Molven et al, 2008); 11 (Rubio-Cabezas et al, 2009);12 (Bonfanti et al, 2009); 13 (Moritani et al, 2013); 14 (Ozturk Mehmet et al, 2014); 15 (Chan et al, 1987); 16 (Gruppuso et al, 1984); 17 (Oohashi et al, 1993); 18 (Yano et al, 1992); 19 (Ozturk Mehmet et al, 2014); 20 (Warren-Perry et al, 1997) 21 (Sakura et al, 1986); 22 (Shoelson et al, 1983a); 23 (Tager et al, 1979). …”

“… References: 1 (Garin et al, 2010); 2 (Raile et al, 2011); 3 (Hussain et al, 2013); 4 (Boesgaard et al, 2010); 5 (Meur et al, 2010); 6 (Edghill et al, 2008); 7 (Stoy et al, 2007); 8 (Polak et al, 2008); 9 (Colombo et al, 2008); 10 (Molven et al, 2008); 11 (Rubio-Cabezas et al, 2009);12 (Bonfanti et al, 2009); 13 (Moritani et al, 2013); 14 (Ozturk Mehmet et al, 2014); 15 (Chan et al, 1987); 16 (Gruppuso et al, 1984); 17 (Oohashi et al, 1993); 18 (Yano et al, 1992); 19 (Ozturk Mehmet et al, 2014); 20 (Warren-Perry et al, 1997) 21 (Sakura et al, 1986); 22 (Shoelson et al, 1983a); 23 (Tager et al, 1979). …”