Table 2.

Genotype–phenotype analysis and follow-up characteristics of mutation positive NDM patients.

Family and patient no.	Gene	Age a (weeks)	GW/BW (weeks/g)	Current age (years)	Site of mutation	DNA (protein) description	Zygosity/novelty	NDM subtype	F/H MD	EPI	Pancreas imaging	SU-R	Associated disease and follow-up
1.1	GCK	4	38/1600	2.4	Exon 5	c.506A>G (p.K169R)	HM/novel	Permanent	Yes	No	Normal	No	Thalassemia major
2.2	GCK	1	40/1900	6.3	Exon 5	c.506A>G (p.K169R)	HM	Permanent	Yes	No	Normal	No	Two siblings (patient 2.3 and 2.4) also had NDM
2.3	GCK	2	40/1700	Died	Exon 5	c.506A>G (p.K169R) b	HM	Permanent b	Yes	NA	Normal	NA	Died due to sepsis at 3 months
2.4	GCK	4	39/1600	Died	Exon 5	c.506A>G (p.K169R) b	HM	Permanent b	Yes	NA	Normal	NA	Died due to intestinal obstruction (post surgery) at 3 months
3.5	GCK	2	40/2400	2.7	Exon 6	c.658T>C (p.C220R)	HM/novel	Permanent	Yes	No	Normal	No	Patient 3.5 and 3.6 are siblings in a large consanguineous family with a number of individuals with monogenic diabetes
3.6	GCK	1	36/1600	1.2	Exon 6	c.658T>C (p.C220R)	HM	Permanent	Yes	No	Normal	No
4.7	6q24 (ZFP57)	1	40/3150	3.0	Exon 6	c.682C>T (p.R228C)	HM/novel	Transient	Yes	No	Normal	NA	Remission at 3 months
5.8	6q24 (ZFP57)	1	40/2200	1.0	Exon 6	c.964delC (p.Q322RfsX13)	HM/novel	Transient	No	No	Normal	NA	Macroglossia, remission at 5 months
6.9	6q24	1	39/1980	Died		Complete loss of methylation	UPDPat6	Transient	No	No	Normal	NA	Remission at 3 months, died when she was 5 months
7.10	PTF1A	1	31/1500	3.1	Promoter	g.23508437A>G	HM	Permanent	Yes	Yes	Agenesis	NA	Developmental delay
8.11	PTF1A	10	39/2400	3.1	Promoter	g.23508437A>G	HM	Permanent	No	Yes	Agenesis	NA
9.12	PTF1A	3	32/1200	2.4	Promoter	g.23508365A>G	HM	Permanent	No	Yes	Agenesis	NA	Neonatal cholestasis
10.13	EIF2AK 3	14	40/3000	Died	Exon 5	c.997C>T (p.Q333X)	HM	Permanent	Yes	No	Hypoplasia	NA	A hepatic failure observed at 12 months old, skeletal dysplasia on X-rays, died at the age of 3 years due to second attack of hepatic failure
11.14	EIF2AK3	12	40/2800	3.3	Exon 9	c.1562G>A (p.W521X)	HM/novel	Permanent	No	No	Normal	NA	No liver dysfunction observed, severe skeletal dysplasia
12.15	EIF2AK3	10	40/3050	1.0	Intron 11	c.1884-1G>C (p.?)	HM/novel	Permanent	Yes	No	Normal	NA	Transient elevation of liver enzymes, hypoalbuminaemia, no skeletal dysplasia at the 1 year of age
13.16	INS	1	35/1910	1.2	Promoter	c.-331C>A (p.?)	HM	Transient	No	No	Normal	NA	Remission at the age of 2 months
14.17	INS	1	37/1400	0.7	Promoter	c.-331C>A (p.?)	HM	Permanent	Yes	No	Normal	NA	No remission
15.18	KCNJ11	2	39/3000	4.8	Exon 1	c.602G>A (p.R201H)	HT	Permanent	Yes	No	Normal	Yes	Successful transfer to SU therapy and weaned off insulin therapy
16.19	KCNJ11	13	40/2800	6.6	Exon 1	c.602G>A (p.R201H)	HT	Permanent	No	No	Normal	Yes	Developmental delay, epilepsy, successful transfer to SU therapy and weaned off insulin therapy
17.20	ABCC8	3	40/2700	2.4	Exon 10	c.1594A>G (p.S532G)	HT/novel	Transient	Yes	No	Normal	NA	Remission at the age of 3 months

GW, gestation week; BW, birth weight; NDM, neonatal diabetes mellitus; HM, homozygous; HT, heterozygous; UPDPat6, paternal uniparental disomy on Chr6q24; F/H MD, family history of monogenic diabetes; EPI, exocrine pancreas insufficiency; SU-R, sulphonylurea response; SU, sulphonylurea.

^aAge at NDM diagnosis.

^bNot tested but presumably GCK PNDM as sibling diagnosed with GCK PNDM and both parents were heterozygous carriers of GCK mutation.