OBJECTIVE: To investigate the clinical features and SLC35A2 variant of a case of congenital disorder of glycosylation type IIm (CDG-IIm), and to identify the possible causes of the disease. METHODS: Trio-whole exome sequencing (WES) was used to analyze the gene variant of the children and their parents. The suspicious gene variants were screened for Sanger verification and the bioinformatics prediction was used to analyze the hazard of variant. RESULTS: The clinical manifestations of the child were epilepsy, global growth retardation, nystagmus, myocarditis and other symptoms. MRI showed brain dysplasia such as wide frontal temporal sulcus and subarachnoid space on both sides. Echocardiography showed left ventricular wall thickening and patent foramen ovale. According to the results of gene detection, there was a heterozygous missense variant c.335C>A (p.Thr112Lys) in SLC35A2 gene. The parents were wild-type at this locus, which was a de novo variant. At the same time, there was no report of this variant in the relevant literature, which was a novel variant in SLC35A2 gene. According to the genetic variant guidelines of American College of Medical Genetics and Genomics, SLC35A2 gene c.335C>A (p.Thr112Lys) variant was predicted to be likely pathogenic (PS2+PM2+PP3). CONCLUSION The variant of SLC35A2 gene c.335C>A(p.Thr112Lys) may be the cause of the disease in the child.
Child ; Congenital Disorders of Glycosylation/genetics* ; Glycosylation ; Humans ; Magnetic Resonance Imaging ; Monosaccharide Transport Proteins/genetics* ; Whole Exome Sequencing

OBJECTIVE: To identify potential mutation of PMM2 gene in an infant with congenital disorders of glycosylation type 1a (CDG-1a). METHODS: Genomic DNA was extracted from peripheral blood sample of the patient. All coding exons (exons 1-8) and splicing sites of the PMM2 gene were amplified with PCR. Potential variants were detected by direct sequencing of the PCR products and comparing the results against the ESP and SNP human gene databases. A protein BLAST system was employed to analyze cross-species conservation of the variants amino acid. A PubMed BLAST CD-search system was employed to identify functional domains damaged by variants of the PMM2 gene. Impact of potential variants was analyzed using software including PolyPhen-2 SIFT and Mutation Taster. Whole exome sequencing was used to identify additional variants of the PMM2 gene which may explain the condition of the patient. RESULTS: The child was found to carry compound heterozygous variants (c.458_462delTAAGA and c.395T>C) of the PMM2 gene, which were inherited respectively from his father and mother. The c.458_462delTAAGA has not been reported previously and may result in disruption of 10 functional domains within the PMM2 protein. The c.395T>C mutation has been recorded by a SNP database with frequency unknown. Both mutations were predicted as "probably damaging". Whole exome sequencing has identified no additional disease-causing variant which can explain the patient's condition. CONCLUSION The patient's condition may be attributed to the compound heterozygous variants c.458_462delTAAGA and c.395T>C of the PMM2 gene. Above results has facilitated molecular diagnosis for the patient.
Congenital Disorders of Glycosylation ; genetics ; Exons ; Humans ; Infant ; Mutation ; Phosphotransferases (Phosphomutases) ; genetics

OBJECTIVETo analyze the clinical and PMM2 gene mutation features of congenital disturbance of glycosylation caused by PMM2 gene mutation (PMM2-CDG, previously known as CDG 1a).

METHODThe clinical data of two Chinese patients who were clinically diagnosed as PMM2-CDG at neurology department of Beijing Children's Hospital in 2012 were retrospectively collected. The gene mutations were identified by Sanger sequencing.

RESULTBoth patients were female, aged 1 year and 1 month and 8 months respectively. The main clinical features of the two cases were developmental delay after birth, chronic diarrhea and metabolic acidosis, associated with elevated serum transaminases, and decreased antithrombin III activity. Physical examination showed esotropia, inverted nipples, and abnormal subcutaneous fat pads. The cranial MRI showed cerebellar atrophy. Both cases were treated with occupational therapy, physical therapy and speech therapy. The development was gradually improved but also delayed as compared with normal peers during follow-up for more than 3 years. Genetic analysis showed that patient 1 was compound heterozygous for c. 422G>A(p.Arg141His), which was reported for known pathogenic mutation, and c. 669C>A(p.Asp223Glu), was a new mutation. The patient 2 showed compound heterozygous mutation for c. 634A>G (p.Met212Val)and c. 713G>C(p.Arg238Pro), which were both new mutations.

CONCLUSIONPMM2-CDG is a rare metabolic disease, and the diagnosis should be considered in a child with developmental delay, elevated serum transaminases, decreased antithrombin III activity, inverted nipples, abnormal subcutaneous fat pads, esotropia, and cerebellar atrophy on MRI. It can be confirmed by PMM2 gene analysis.

Asian Continental Ancestry Group ; Congenital Disorders of Glycosylation ; genetics ; DNA Mutational Analysis ; Developmental Disabilities ; Female ; Genetic Testing ; Glycosylation ; Heterozygote ; Humans ; Infant ; Magnetic Resonance Imaging ; Mutation ; Phosphotransferases (Phosphomutases) ; genetics ; Retrospective Studies