Cytogenetic and molecular characterization of a patient with partial 6q trisomy and 1q monosomy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze a girl with moderate mental retardation and speech and language disorders with cytogenetics technique and next-generation sequencing (NGS).</p><p><b>METHODS</b>G-banding chromosome analysis was used to ascertain the karyotype of the child and her parents, and NGS was used for determining the size and origin of the abnormal chromosome fragment. Mate-pair and PCR were used to determine its parental origin.</p><p><b>RESULTS</b>The karyotype of the child was determined to be 46,XX,add(1)(q44)dn, while her parents were both normal. NGS revealed that the child has harbored a partial trisomy of 6q24.3-q27, and the breakpoint was mapped to at 6q24.3q27. In addition, a 2.5 Mb microdeletion at 1q44 was found in the patient.</p><p><b>CONCLUSION</b>No recognizable phenotype was associated with 1q44 deletion. The abnormal phenotypes presented by the child may be attributed to the 6q24.3-q27 triplication. Compared with conventional cytogenetic analysis, NGS has a much higher resolution and great accuracy.</p>

Clinical and genetic analysis of a Chinese family affected with X-linked Charcot-Marie-Tooth disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the clinical manifestations and identify causative mutations for a Chinese family affected with X-linked Charcot-Marie-Tooth disease.</p><p><b>METHODS</b>Clinical, electrophysiological and pathological features of the family were carefully analyzed by neurologists. Blood samples were obtained from the proband and other family members. Genomic DNA was extracted. Mutation analysis of GJB1 gene was analyzed with PCR and direct sequencing.</p><p><b>RESULTS</b>The family has fit with X-linked inheritance, and the affected individuals have typical clinical manifestations. A c.614A>G (p.Asn205Ser) mutation was detected in the GJB1 gene in all affected individuals in the family.</p><p><b>CONCLUSION</b>A c.614A>G (p.Asn205Ser) mutation of GJB1 gene is co-segregated with the disease phenotype in this family and probably underlies the disease.</p>

Analysis of gene mutation in a family featuring autosomal dominant May-Hegglin anomaly / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze clinical features and mutation in MYH9 gene for a family featuring autosomal dominant May-Hegglin anomaly.</p><p><b>METHODS</b>Clinical and pathological features of all family members were analyzed. Blood samples were collected from the proband and other family members, and genomic DNA was extracted. Potential mutations of MYH9 gene exons 10, 25, 26, 30, 38 and 40 were screened with PCR and direct sequencing. After a mutation was identified in the proband, other affected members as well as healthy members from this family were analyzed with a pair of primers to amplify the mutant site. The PCR products were digested with Taq I enzyme and analyzed with agarose gel electrophoresis.</p><p><b>RESULTS</b>All affected members had bleeding tendency and typical features including giant platelets, thrombocytopenia and characteristic Dohle body-like leukocyte inclusions. A heterozygous missense mutation c.5521G>A (p.Glu1841Lys) in exon 38 of the MYH9 gene was identified in all affected members from this family.</p><p><b>CONCLUSION</b>The variant, c.5521G>A (p.Glu1841Lys) of MYH9, has co-segregated with the phenotype in the family. The mutant site is a hot spot in Chinese population.</p>

Novel deletion of SPAST in a Chinese family with hereditary spastic paraplegia

<p><b>INTRODUCTION</b>Hereditary spastic paraplegia (HSP) belongs to a large, heterogeneous group of progressive neurodegenerative diseases characterised by progressive lower extremity weakness and spasticity, which is caused by developmental failure or degeneration of motor axons in the corticospinal tract. Classical genetic studies have identified at least 46 genetic loci responsible for HSP.</p><p><b>METHODS</b>A genetic study was conducted on a four-generation Chinese family with autosomal dominant HSP. The SPAST gene was investigated using linkage analysis and direct sequencing. Findings were compared with unaffected family members and 50 normal, unaffected individuals who were matched for geographical ancestry.</p><p><b>RESULTS</b>We identified a novel 14-bp heterozygous deletion that induced a frameshift mutation in exon 15 of SPAST (SPG4). This mutation is predicted to have functional impact and found to cosegregate with the disease phenotype.</p><p><b>CONCLUSION</b>Our results have expanded the mutation spectrum of the SPAST gene. These findings could help clinicians provide prenatal diagnosis of affected foetuses in families with a known history of such neurodegenerative diseases.</p>