HPDL deficiency causes a neuromuscular disease by impairing the mitochondrial respiration.

Mitochondrial diseases are caused by variants in both mitochondrial and nuclear genomes. A nuclear gene HPDL (4-hydroxyphenylpyruvate dioxygenase-like), which encodes an intermembrane mitochondrial protein, has been recently implicated in causing a neurodegenerative disease characterized by pediatric-onset spastic movement phenotypes. Here, we report six Chinese patients with bi-allelic HPDL pathogenic variants from four unrelated families showing neuropathic symptoms of variable severity, including developmental delay/intellectual disability, spasm, and hypertonia. Seven different pathogenic variants are identified, of which five are novel. Both fibroblasts and immortalized lymphocytes derived from patients show impaired mitochondrial respiratory function, which is also observed in HPDL-knockdown (KD) HeLa cells. In these HeLa cells, overexpression of a wild-type HPDL gene can rescue the respiratory phenotype of oxygen consumption rate. In addition, a decreased activity of the oxidative phosphorylation (OXPHOS) complex II is observed in patient-derived lymphocytes and HPDL-KD HeLa cells, further supporting an essential role of HPDL in the mitochondrial respiratory chain. Collectively, our data expand the clinical and mutational spectra of this mitochondrial neuropathy and further delineate the possible disease mechanism involving the impairment of the OXPHOS complex II activity due to the bi-allelic inactivations of HPDL.

[Two novel RUNX2 gene mutations in two Chinese families with cleidocranial dysplasia].

OBJECTIVE: To identify the RUNX2 gene mutation in two unrelated Chinese families with cleidocranial dysplasia (CCD), and to assess the feasibility of gene diagnosis for patients with CCD. METHODS: Genomic DNA was isolated from peripheral blood samples of 4 patients and 4 healthy members in the two pedigrees as well as 102 unrelated healthy controls. All 7 coding exons and their flanking intronic sequences of the RUNX2 gene were amplified by PCR, then the PCR products were sequenced bi-directionally. The sequencing results were compared with normal sequences in GenBank to identify the mutation. The mutation was confirmed by RFLP with restriction endonuclease. RESULTS: In one family, a novel heterozygous missense mutation c.346T to A (W116R) in exon 1 of the RUNX2 gene was detected in the two affected individuals, and the mutation was further confirmed with Bsr I restriction endonuclease digestion. In the other family, a novel nonsense mutation c.610A TO T (K204X) was identified in the two patients. No above sequence change was found in the 102 healthy controls. CONCLUSION: Two novel RUNX2 mutations were found in two unrelated Chinese families with cleidocranial dysplasia. The identification of these mutations further extended the mutation spectrum of RUNX2 gene and will facilitate prenatal diagnosis and gene diagnosis of CCD.

[Multi-central randomized controlled investigation on the massage for supplementing qi and removing obstruction in the Governor Vessel for treatment of infantile diarrhea due to spleen deficiency].

OBJECTIVE: To make multi-central clinical evaluation of the massage for supplementing qi and removing obstruction in the Governor Vessel for treatment of infantile diarrhea due to spleen deficiency. METHODS: By using multi-central, randomized and controlled method, 275 cases were randomly divided into an observation group (n = 137) and a control group (n = 138). The observation group were treated by the massage for supplementing qi and removing obstruction in the Governor Vessel, and the control group by routine massage therapy in Tuina Science, a teaching material for college and school of TCM. After treatment for 7 days, their therapeutic effects were compared. RESULTS: The cured rate was 83.2% in the observation group and 69.6% in the control group with a signifi cant difference between the two groups (P < 0.05), the former being better than the latter. The mean cured time was (3.22 +/- 1.04) days in the observation group and (4.20 +/- 1.11) days in the control group with a significant difference between the two groups (P < 0.05), the former being shorter than the latter. CONCLUSION: The massage for supplementing qi and removing obstruction in the Governor Vessel has a definite therapeutic effect on infantile diarrhea due to spleen deficiency, with rapid effect.