OBJECTIVETo analyze a girl with moderate mental retardation and speech and language disorders with cytogenetics technique and next-generation sequencing (NGS).

METHODSG-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.

RESULTSThe 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.

CONCLUSIONNo 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.

Adult ; Child ; Chromosome Banding ; Chromosome Disorders ; genetics ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Male ; Monosomy ; genetics ; Trisomy ; genetics

INTRODUCTIONHereditary 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.

METHODSA 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.

RESULTSWe 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.

CONCLUSIONOur 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.

Adenosine Triphosphatases ; genetics ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; China ; Exons ; Family Health ; Female ; Frameshift Mutation ; Gene Deletion ; Genetic Linkage ; Genetic Predisposition to Disease ; Heterozygote ; Humans ; Infant ; Male ; Middle Aged ; Pedigree ; Phenotype ; Sequence Analysis, DNA ; Spastic Paraplegia, Hereditary ; diagnosis ; genetics ; Spastin ; Young Adult

OBJECTIVETo study the clinical manifestations and identify causative mutations for a Chinese family affected with X-linked Charcot-Marie-Tooth disease.

METHODSClinical, 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.

RESULTSThe 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.

CONCLUSIONA c.614A>G (p.Asn205Ser) mutation of GJB1 gene is co-segregated with the disease phenotype in this family and probably underlies the disease.

Asian Continental Ancestry Group ; genetics ; Charcot-Marie-Tooth Disease ; genetics ; Child ; Connexins ; genetics ; Female ; Genes, X-Linked ; genetics ; Genetic Diseases, X-Linked ; genetics ; Humans ; Male ; Mutation ; Pedigree

OBJECTIVETo analyze clinical features and mutation in MYH9 gene for a family featuring autosomal dominant May-Hegglin anomaly.

METHODSClinical 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.

RESULTSAll 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.

CONCLUSIONThe 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.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Exons ; Female ; Genes, Dominant ; Hearing Loss, Sensorineural ; Humans ; Male ; Molecular Motor Proteins ; genetics ; Mutation ; Myosin Heavy Chains ; genetics ; Pedigree ; Phenotype ; Thrombocytopenia ; diagnosis ; genetics

Objective:To evaluate the clinical value of color Doppler ultrasound(CDUS) combined with vascular enhancement technology(VET) in diagnosis of iliac vein compression syndrome(IVCS).Methods:From Jan 2016 to Oct 2018, 252 patients with the lower extremities chronic venous diseases(CVD) were selected in the Second Hospital of Hebei Medical University. The ipsilateral iliac veins of the affected limbs were examined by CDUS, VET and the combined diagnosis of IVCS before X-Ray venography(XRV). Iliac vein diameter stenosis ratio(DSR)>50% in transverse section was the criterion of ultrasound diagnosis of IVCS. The stenosis site of iliac vein and indirect signs of IVCS, such as presence of collateral circulation and the retrograde flow of internal iliac vein were recorded. The cases, which had the same results in CDUS, VET and both and XRV, were divided into IVCS group and non-IVCS group. The results of XRV were taken as the gold standard, the diagnostic efficiency of the above 3 methods in diagnosis of IVCS was calculated. The cases identically diagnosed by the most effective ultrasonic method and XRV were divided into DVT group and non-DVT group according to the deep vein thrombosis in lower limbs. In the non-DVT group, there were five groups of C2-C6 on the basis of the CEAP clinical grades of CVD in lower extremity. The relationship between IVCS and different CEAP clinical grades were analyzed. The locations of common iliac vein stenosis and collateral circulation formation and internal iliac vein reverse flow were evaluated for the diagnosis of the IVCS.Results:①XRV diagnosis of IVCS was used as the gold standard. Compared with CDUS and VET alone, the sensitivity and specificity of CDUS combined with VET was the highest(all P<0.05). ②The distribution of DVT and non-DVT was significantly different in IVCS group and non-IVCS group diagnosed by the CDUS combined with VET(χ 2=145.0, P<0.001). ③In the non-DVT group, statistically significant differences of grades C3 and C5 were found between IVCS group and non-IVCS group(all P<0.05), while the differences of grades C2, C4 and C6 were non-significant(all P>0.05). ④For the proportion of the iliac vein stenosis sites, the prevalence of the primary section of left common iliac vein was much higher than those of the primary section of right common iliac vein and the middle-distal sections of bilateral common iliac veins(all P<0.05). There was no statistical difference between the middle-distal section of bilateral common iliac veins, and nor was bilateral junction area between external iliac vein and common femoral vein(all P>0.05). ⑤In IVCS group, which had the same results of CDUS combined with VET and XRV, there were statistical differences in the positive rate of collateral circulation and the retrograde flow of internal iliac vein(χ 2=6.717, P=0.010), and the former is higher than the latter. Conclusions:CDUS combined with VET has a higher diagnostic efficiency for IVCS than VET or CDUS alone. The presence of IVCS is closely related to DVT of lower extremities, but not related to clinical class of CEAP. The most common site of IVCS is the initial segment of the left common iliac vein. The presence of collateral circulation can be used as indirect indicators for the diagnosis of IVCS.