Clinical and genetic analysis of five pedigree with maturity-onset diabetes of the young type 2 / 中华内分泌代谢杂志

Objective:To explore the clinical and molecular genetic characteristics of patients with maturity-onset diabetes of the young type 2(MODY2).Methods:Clinical data and laboratory results were collected from five MODY2 patients and their family members diagnosed in the Department of Endocrinology, Genetics, and Metabolism of Xi ′an Children′s Hospital in the recent two years. Whole exome sequencing was carried out on every proband to identify potential variants, then the suspected variants were verified with Sanger sequencing in family numbers.Results:Among the 5 probands, except for proband 4 who presented with polydipsia and polyuria, hyperglycemia in the rest of the children was accidentally identified. Urine routine, urinary protein, and blood lipid of the five probands were all normal, and HbA 1C was between 5.96% and 8.15%. Moreover, an important discovery in this study was that proband 5 had insulin resistance(IRS), which was different from previous studies. It was confirmed by genetic analysis that a glucokinase(GCK) gene variant existed in every MODY2 pedigree. There were four GCK variants in this study, including c. 146C>T(p.T49I), c. 1237T>G(p.Y413D), c. 683C>T(p.T228M) and c. 952G>T(p.G318W), among which the C. 1237T>G(P.y413d) and C. 952G>T(P.G318W) had not been reported till now. All probands received lifestyle intervention, and the blood glucose control was relatively stable. Conclusion:There is MODY2 patient complicated with IRS. MODY2 patients can be controlled well by lifestyle interventions. In addition, we discovered two novel variants of GCK, which extend the mutation spectrum of this gene.

Clinical and genetic analysis of an infant with permanent neonatal diabetes mellitus due to novel variant of insulin gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for an infant with permanent neonatal diabetes mellitus (PNDM).@*METHODS@#Clinical data of the child was collected. Targeted capture-next generation sequencing was carried out to identify the potential variants. Candidate variant was verified by Sanger sequencing of her family members.@*RESULTS@#The child was a 4-month-and-26-day female featuring onset of ketoacidosis accompanied with fasting blood glucose of 24.4 mmol/L, positive urine glucose, decreased serum C-peptide, HbA1c of 9.58%, and negative diabetes autoantibody. Genetic testing revealed that she has carried a heterozygous c.314T>G (p.L105R) variant of the INS gene. Sanger sequencing verified that neither of her parents has carried the same variant, which was also unreported in the literature. The variant was classified as likely pathogenic based on the ACMG guidelines.@*CONCLUSION@#The c.314T>G (P.L105R) variant of the INS gene probably underlay the genetic etiology in this child. Genetic testing should be conducted for children with suspected PNDM for early diagnosis and appropriate treatment.

Analysis of clinical phenotype and genotype of cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome caused by a novel variant of SNAP29 gene / 中华神经科杂志

Objective:To investigate the clinial phenotype and genetic characteristics of a child with cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma (CEDNIK) syndrome and to improve the clinicians′ understanding of this disease.Methods:Clinical data of the child with CEDNIK syndrome diagnosed in Department of Endocrinology, Genetics and Metabolism, Xi′an Children′s Hospital in June 2020 were collected. Whole exome sequencing was carried out to identify the potential variants of SNAP29 gene. Suspected variants were verified by Sanger sequencing of family numbers. The literature about the cases of CEDNIK syndrome were reviewed.Results:The proband is a boy, who was aged 1 year and 4 months, had the manifestations of psychomotor retardation, microcephaly, feeding difficulties, severe malnutrition, recurrent respiratory tract infection, binocular esotropia, sensorineural deafness, cutaneous ichthyosis and keratosis, left cryptorchidism. Brain magnetic resonance imaging indicated congenital dysplasia. Whole exome sequencing identified a homozygous variant of c.383dupT (p.E129Rfs *5) in the SNAP29 gene of the proband, and the heterozygous variation was observed at the same locus in his parents, which conformed to the autosomal recessive inheritance. This mutataion was determined as a pathogenic mutation according to the guidelines of American College of Medical Genetics and Genomics. Literature retrieval showed currently a total of 29 cases of CEDNIK syndrome were reported, containing 8 types of SNAP29 gene mutation. However, there was no Chinese case reported. And the c.383dupT (p.E129Rfs *5) mutation found in this study was a novel one which had not been reported yet. Conclusion:The phenotype of the proband is generally consistent with the CEDNIK syndrome and the novel c.383dupT (p.E129Rfs *5) mutation of SNAP29 gene is the genetic cause.

Identification of a novel variant of SRD5A2 gene in a child featuring steroid 5α-reductase type 2 deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic basis of a child with 5α-reductase type 2 deficiency.@*METHODS@#Clinical data of the child was retrospectively analyzed. Targeted capture-next generation sequencing and Sanger sequencing were carried out to detect potential variants.@*RESULTS@#The patient's main features included micropenis and hypospadia. He was found to harbor compound heterozygous c.680G>A (p.R227Q) and c.3G>T (p.M1I) variants of the SRD5A2 gene. Among these, c.680G>A (p.R227Q) was inherited from his father and was a known pathogenic mutation, while c.3G>T (p.M1I) was inherited from his mother and was unreported previously.@*CONCLUSION@#The compound heterozygous variants of the SRD5A2 gene probably underlay the disease in this child, who was eventually diagnosed with 5α-reductase 2 deficiency.