Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report.

BACKGROUND: Duchenne muscular dystrophies (DMDs) are X-linked recessive neuromuscular disorders with malfunction or absence of the Dystrophin protein. Precise genetic diagnosis is critical for proper planning of patient care and treatment. In this study, we described a Chinese family with mosaic DMD mutations and discussed the best method for prenatal diagnosis and genetic counseling of X-linked familial disorders. METHODS: We investigated all variants of the whole dystrophin gene using multiple DNA samples isolated from the affected family and identified two variants of the DMD gene in a sick boy and two female carriers by targeted next generation sequencing (TNGS), Sanger sequencing, and haplotype analysis. RESULTS: We identified the hemizygous mutation c.6794delG (p.G2265Efs*6) of DMD in the sick boy, which was inherited from his mother. Unexpectedly, a novel heterozygous mutation c.6796delA (p.I2266Ffs*5) of the same gene, which was considered to be a de novo variant, was detected from his younger sister instead of his mother by Sanger sequencing. However, further NGS analysis of the mother and her amniotic fluid samples revealed that the mother carried a low-level mosaic c.6796delA mutation. CONCLUSIONS: We reported two different mutations of the DMD gene in two siblings, including the novel mutation c.6796delA (p.I2266Ffs*5) inherited from the asymptomatic mosaic-carrier mother. This finding has enriched the knowledge of the pathogenesis of DMD. If no mutation is detected in obligate carriers, the administration of intricate STR/NGS/Sanger analysis will provide new ideas on the prenatal diagnosis of DMD.

[Mutational analysis of the methyl-CpG-binding protein 2 (MECP2) gene in male autism patients].

OBJECTIVE: To investigate mutations in the methyl-CpG-binding protein 2 (MECP2) gene in male autism patients by PCR, denaturing high-performance liquid chromatography (DHPLC) and sequencing to explore the role of mutations in MECP2 in autism patients. METHODS: We recruited DNA samples from 44 male autism patients who matched the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DMS-IV) standards. DHPLC was used to screen the mutations in MECP2 gene, and DNA sequencing was performed for the samples with positive DHPLC results. The family members were further investigated in the patients with missense mutations in MECP2 gene. RESULTS: Four cases were found to have mutations in MECP2 gene, including missense mutations of c.590C>T(T197M)in one case and c.602C>T(A201V)in one case, and synonymous mutations of c.1053C>G in one case and c.897C>T in one case. In addition, we found C>T variation in intron 3 at the +74 bp before exon 4, a SNP (rs2071569) usually detected in Chinese population. In the case with c.602C>T(A201V)mutation, his mother and maternal grandfather had the same mutation. His mother had normal phenotype, but his maternal grandfather had depressive disease. CONCLUSION: Mutations in MECP2 are present in male autism patients with relatively higher prevalence, suggesting that these mutations may play roles in the pathogenesis of autism.

Perinatal occipital lobe injury in children: analysis of twenty-one cases.

This study used magnetic resonance imaging to analyze causes and clinical courses of pediatric occipital lobe injury. Patients undergoing magnetic resonance imaging for suspected bilateral occipital lobe injury at our Neurodevelopmental Department between July 2007 and June 2011 were included. We evaluated magnetic resonance imaging characteristics, clinical courses, electroencephalogram monitoring, and Denver Development Screen Test scores. Twenty-one infants were examined. Of these, 10 had been born preterm. Thirteen patients demonstrated hypoglycemia. Perinatal period hypoglycemia comprised the most common cause (71.4%) of occipital brain injury. Visual abnormalities were evident in 18 patients. Seventeen (80.9%) patients manifested epilepsy. Infantile spasms were observed in 13 cases (76.5%). According to Denver Development Screen Test assessment, 17 patients demonstrated delayed motor development. Motor function and language improved in 10 patients after effective control of their seizures. Hypoglycemia constitutes the most common cause of occipital injury in infants. Visual impairment, startle episodes, infantile spasms, and motor developmental delay comprise the most common complications, whereas language function is usually spared.