Maturity onset diabetes of the young (MODY) in Chinese children: genes and clinical phenotypes.

Background To investigate the clinical and molecular characteristics of Chinese children with maturity onset diabetes of the young (MODY). Methods A total of 42 Chinese patients suspected MODY referred to our unit from 2014 to 2018 were enrolled. Mutational analysis of monogenic diabetes mellitus genes was performed by next-generation sequencing and confirmed by Sanger sequencing. Results There were 28 males (66.7%) and 14 females (33.3%) with a mean age of 9.49 ± 3.46 years (range, 1.4-15.3 years) and a mean birth weight of 3.38 ± 0.49 kg (range, 2.55-4.90 kg). Among these patients, 15 patients had polyuria, polydipsia or weight loss. Two patients (4.8%) were obese and six (14.3%) were overweight. Moreover, 13 patients (30.9%) had a family history of diabetes. Thirty variants were identified in 28 patients. Twenty-six variants in 25 patients were pathogenic or likely pathogenic genes (59.5%, 25/42), including 15 patients (60.0%, 15/25) with GCK mutation, four (16.0%, 4/25) with PAX4 mutation, three (12.0%, 3/25) with HNF4A mutation, one (4.0%, 1/25) with INS mutation, one (4.0%, 1/25) with NEUROD1 mutation and one (4.0%, 1/25) with HNF1A mutation. Nine mutations (36.0%, 9/25) were novel. There was no difference between mutation-suspected patients and MODY-confirmed patients except for a 2-h glucose increment in an oral glucose tolerance test (OGTT), while the GCK-MODY had lower glycated hemoglobin (HbA1c) and a significantly smaller 2-h glucose increment in an OGTT compared with transcription factor MODYs. The GCK-MODY was identified by incidental hyperglycemia without glycosuria. GCK-MODY without drug management and hepatocyte nuclear factor-1 alpha (HNF4A) or HNF1A-MODY with sulfonylurea therapy obtained good glucose controlling. Conclusions Mutation of the GCK gene is the most common in MODY patients in China followed by PAX4. The screening criteria can improve the cost-effectiveness of disease diagnosis and treatment. A precise molecular diagnosis would lead to optimal treatment of the patients.

Analysis of clinical and genetic characteristics of 20 cases of children with Silver Russell syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To improve the accuracy of the diagnosis of the disease on the basis of the clinical features and genetic characteristics of patients with Silver Russell syndrome (SRS).</p><p><b>METHOD</b>Patients diagnosed with SRS by Price criteria in 2006 to 2011 were reviewed for their clinical manifestations, physical signs, laboratory examinations and treatments.</p><p><b>RESULT</b>Twenty cases with SRS were 0.08-12.17 yr old. Fifteen were male and 5 were female. The clinical characteristics included more than 80% of cases had postnatal growth retardation 100% (20/20), craniofacial dysmorphism 100% (20/20), small for gestation age 95% (19/20), asymmetry and thinning of the face and/or limbs 90% (18/20), fifth finger clinodactyly 80% (16/20), BMI < -2 SDS 80% (16/20). Their height was obviously lagging behind in the bone age. HD SDS/average of bone retardation was 3.08. The two patients with the chief complaint of external genital abnormalities would have aggressive surgical treatment and they did not use the growth hormone (GH) treatment. Only six patients had used the GH treatment. GH treatment at a dose of 0.1 IU/(kg·d) used in 2 cases achieved a growth velocity (GV) 8 - 11 cm/yr but in another 2 cases < 5 cm/yr. In genetic study, 6 patients were found to have 11p15 low methylation, 1 had low and high methylation, 1 had duplication, no relation between clinical and methylation of 11p15 was found.</p><p><b>CONCLUSION</b>There were great variations of clinical features in SRS characterized by small for gestation age and/or postnatal growth retardation, craniofacial dysmorphism, asymmetry of the face and/or limbs or ultrafine limbs, fifth finger clinodactyly. Severely low BMI was seen and height was obviously lagging behind in the bone age. The findings of laboratory tests and imaging of SRS were not specific. Some of SRS had 11p15 imprinting defects. The treatment of SRS is mainly symptomatic.</p>