Rabson-Mendenhall syndrome caused by a novel splice-site mutation (c.1123+2 T>C) of insulin receptor: A case report and review of literature

Table 1 Results of the follow-up in the past 5 years

Time	Fasting C-peptide (ng/mL)	Postprandial C-peptide (ng/mL)	Fasting insulin (IU/mL)	Postprandial insulin (IU/mL)	HbA1c	Urine sugar	Urine ketone bodies
2011	8.09	25.32	272.4	> 1000	5.6%	+	+
2019	7.67	22.37	328.36	327.99	8.6%	3+	4+
2022	7.17	20.2	> 200	> 200	13%	4+	4+
2023	4.9	17.8	> 200	> 200	12.6%	3+	4+
2024	4.5	16.7	> 200	> 200	11.2%	3+	4+
2025	3.07	14.3	> 200	> 200	11.5%	2+	3+

HbA1c: Glycated hemoglobin A1c.

Table 2 The secondary structures of the two splice mutation modes proteins, n (%)

Mutation	Total amino acid, n	α-helix	β-fold	β-turn	Random coil
Wild-type	1382	299 (21.64)	249 (18.02)	52 (3.76)	782 (56.58)
MT1	329	59 (17.93)	52 (15.81)	11 (3.34)	207 (62.92)
MT2	394	86 (21.83)	62 (15.74)	14 (3.55)	232 (58.88)

MT: Mutant type.

Table 3 Insulin receptor mutations and clinical feature of Rabson-Mendenhall syndrome patients

Mutation type	Amin acid change	Clinical feature	Ref.
Missense	Pro193 Leu	Low birth weight, failure to thrive, hypotrichosis, clitoromegaly, and relatively coarse facies	Carrera et al[30]
Missense	Ile116Thr/Arg1131Trp	Early extreme hyperinsulinemia that declines over time; severe insulin resistance, growth retardation, acanthosis nigricans, dental anomalies, hyperglycemia and ketoacidosis risk	Longo et al[31]
Missense	Pro970Thr/Arg1131Trp	Hyperinsulinemia, growth retardation, acanthosis, dental anomalies, early-onset diabetes	Longo et al[32]
Missense	Asn878Ser/Ala1162Val	Severe insulin resistance with marked hyperinsulinemia, acanthosis, growth delay, dysmorphic dentition; refractory hyperglycemia requiring multi-drug and high-dose insulin therapy	Moreira et al[33]
Missense	Cys159Phe/Arg229Cys	Extreme insulin resistance, short stature, severe acanthosis, hypertrichosis, dental abnormalities, early-onset hyperglycemia	Thiel et al[34]
Missense	Arg209His/Gly359Ser	Markedly reduced receptor, extreme insulin resistance, short stature, severe acanthosis, hypertrichosis, dental anomalies, early diabetes, recurrent infections	Tuthill et al[35]
Missense	Arg86Term; Asp261-Leu262 Ins Leu His Val	Severe insulin resistance, hyperinsulinemia, growth retardation, acanthosis nigricans, dental dysplasia, early-onset diabetes	Müller-Wieland et al[36]
Missense/deletion	IVS4-2 A>G/c.2480-2487del	Profound insulin resistance, hyperinsulinemia, failure to thrive, acanthosis, dental and nail abnormalities, early-life diabetes	Kadowaki et al[37]
Missense	Cys279Arg	Child with RMS: Extensive acanthosis nigricans, skin tags, hypertrichosis, short stature, abdominal distension, clitoromegaly, hyperinsulinemia and hyperglycemia	Duraiswamy et al[38]
Missense/deletion	Arg145Cys/19p13.2del 237kbp	Adult RMS misdiagnosed as T1DM: Severe insulin resistance, malnutrition/Low BMI, acanthosis, prognathism, dysmorphic features, diabetic complications (retinopathy)	Almotawa et al[39]
Missense/deletion	Pro1131Arg/c.4007_4010delAGAG	Infant with generalized acanthosis, growth retardation, dysmorphism, hypertrichosis, fasting hypoglycemia with hyperinsulinemia	Yan et al[40]
Missense	Arg1119Trp/del243Kb(chr19:7150507-7152938)	Severe insulin resistance, hyperinsulinemia, growth retardation, acanthosis, dental anomalies, early diabetes	Chen et al[41]
Missense	Arg141Trp	Marked hyperinsulinemia, acanthosis, growth failure, dental/skin findings, insulin-resistant diabetes requiring complex therapy	Bastaki et al[42]

Pro: Proline; Leu: Leucine; Ile: Isoleucine; Thr: Threonine; Arg: Arginine; Trp: Tryptophan; Asn: Asparagine; Ser: Serine; Ala: Alanine; Val: Valine; Cys: Cysteine; Phe: Phenylalanine; His: Histidine; Term: Termination; Asp: Aspartic acid; Ins: Insertion; His: Histidine; RMS: Rabson-Mendenhall syndrome; T1DM: Type 1 diabetes mellitus; BMI: Body mass index.