Identification of a recurrent mutation in the ROR2 gene in a Chinese family with brachydactyly type B / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the disease-causing mutation in a Chinese family with brachydactyly type B (BDB).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples of family members. Exons 8 and 9 of the ROR2 gene were amplified by polymerase chain reaction (PCR) and sequenced directly. Furthermore, the PCR products showing mutation were cloned into pMD18T vector and the insert fragments were sequenced.</p><p><b>RESULTS</b>A 1398-1399 insA heterozygous mutation was detected in the patient. This mutation had been found in German families with BDB.</p><p><b>CONCLUSION</b>To the authors' knowledge, it is the first report on identification of the ROR2 pathogenic mutation in Chinese patients with BDB.</p>

Heterogeneous phenotypes in Chinese glycogen storage disease type Ia patients with homozygous G727T mutation / 中华儿科杂志

<p><b>UNLABELLED</b>Glycogen storage disease (GSD) type Ia is an autosomal recessive disorder caused by a deficiency of glucose-6-phosphatase (G6Pase). The gene that encodes G6Pase was mapped to 17q21. The molecular genetic basis of GSD type Ia in the mainland Chinese population has not been explored.</p><p><b>OBJECTIVE</b>To analyze the G6Pase gene mutations, and to compare the phenotypic features and the response to the corn starch treatment among patients who share the same mutation.</p><p><b>METHODS</b>With the consent of the parents and their children, the authors studied 18 families with clinically diagnosed GSD type Ia from our long time follow-up groups. Direct DNA sequencing of all 5 exons and the exon-intron boundaries of G6Pase gene were done on the blood specimens. Seven of the 18 patients, male 2 and female 5, aged 1.5 to 16 years, were homozygous for same mutation. The clinical symptoms, signs and the serum biochemical values before and after treatment were compared in these 7 patients.</p><p><b>RESULTS</b>The 7 patients were homozygous of G-->T transversion at the nucleotide 727 in exon 5 (G727T), which has previously been reported to cause abnormal splicing. The parents were heterozygous of the G727T mutation. All the patients exhibited typical features of GSD type Ia with variable severity, including hypoglycemia, hepatomegaly, kidney enlargement, growth retardation, bleeding diathesis, lactic acidemia, hyperlipidemia, and hyperuricemia. Two of the patients had repeated hypoglycemic seizures before the age of 2 years. One had moderate splenomegaly when he came to our clinic at the age of 16, the spleen size was reduced to 2 cm below the left costal margin after 5-year treatment. His sister, homozygous of G727T, did not show splenomegaly. One had multiple hepatic adenoma since the age of 5 years. Four had 5-year-delayed bone age when they started treatment at the age of 9 to 16 years, the bone age reached normal after 2 - 3 years treatment. No matter when they started corn starch treatment, the height increase in the first year was most obvious with an average of 10 cm. All the patients had abnormal liver function before treatment, 5 had constant slightly elevated liver enzymes with the treatment. All had normal urinalysis test, but the urine beta(2)- microglobulin was elevated.</p><p><b>CONCLUSIONS</b>G727T mutation may be the major cause of GSD type Ia in China. Patients with the same mutation could have variable phenotypic characteristics, and the response to the corn starch treatment was different. The diagnosis of GSD type Ia can be based on clinical and biochemical abnormalities combined with mutation analysis instead of enzyme assays on liver biopsy.</p>