OBJECTIVE: To screen for mutations of fragile X mental retardation 1 (FMR1) gene during early and middle pregnancy and provide prenatal diagnosis for those carrying high-risk CGG trinucleotide expansions. METHODS: Peripheral blood samples of 2316 pregnant women at 12 to 21(+6) gestational weeks were collected for the extraction of genomic DNA. CGG repeats of the FMR1 gene were detected by fluorescence PCR and capillary electrophoresis. Genetic counseling and prenatal diagnosis were provided for 3 women carrying the premutations. RESULTS: The carrier rate of CGG repeats of the FMR1 gene was 1 in 178 for the intermediate type and 1 in 772 for the premutation types. The highest frequency allele of CGG was 29 repeats, which accounted for 49.29%, followed by 30 repeats (28.56%) and 36 repeats (8.83%). In case 1, the fetus had a karyotype of 45,X, in addition with premutation type of CGG expansion of the FMR1 gene. Following genetic counseling, the couple chose to terminate the pregnancy through induced labor. The numbers of CGG repeats were respectively 70/- and 29/30 for the husband and wife. In case 2, amniocentesis was performed at 20 weeks of gestation. The number of CGG repeats of the FMR1 gene was 29/-. No abnormality was found in the fetal karyotype and chromosomal copy number variations. The couple chose to continue with the pregnancy. Case 3 refused prenatal diagnosis after genetic counseling and gave birth to a girl at full term, who had a birth weight of 2440 g and no obvious abnormality found during follow-up. CONCLUSION Pregnant women should be screened for FMR1 gene mutations during early and middle pregnancy, and those with high-risk CGG expansions should undergo prenatal diagnosis, genetic counseling and family study.
DNA Copy Number Variations ; Female ; Fragile X Mental Retardation Protein/genetics* ; Fragile X Syndrome/genetics* ; Genetic Counseling ; Humans ; Mutation ; Pregnancy ; Trinucleotide Repeat Expansion ; Trinucleotide Repeats

Adult ; Ataxin-1 ; genetics ; DNA Mutational Analysis ; Family Health ; Female ; Humans ; Male ; Middle Aged ; Pedigree ; Spinocerebellar Ataxias ; diagnosis ; genetics ; Trinucleotide Repeat Expansion ; genetics

OBJECTIVETo explore the clinical and genetic characteristics of patients with dentatorubro-pallidoluysian atrophy (DRPLA).

METHODSDNA analysis for DRPLA gene was performed in two patients. Clinical features and genetic testing of Chinese DRPLA patients reported in the literature were reviewed in terms of initial symptoms, CAG repeat and age of onset.

RESULTSBoth families were confirmed by genetic analysis. In family 1, the number of CAG repeat in the proband, his brother and his mother was determined respectively as 8/65, 8/53 and 8/18. In family 2, the number of CAG repeat was respectively 13/63, 13/18, 18/52 and 13/13 in the proband, his brother, his father and his mother. The size of the expanded CAG repeats has inversely correlated with the age at onset (P<0.05, r=- 0.555). The age at onset of epilepsy was 10 and that for the onset of ataxia is forty years in initial symptom.

CONCLUSIONThe clinical characteristics of DRPLA include epilepsy, ataxia and cognitive impairment. The initial symptoms are epilepsy in adolescence and ataxia in adults. The size of expanded CAG repeats inversely correlates with the age at onset. The initial symptoms are different with different age of onset. It is difficult to diagnose DRPLA at an early stage.

Adolescent ; Adult ; Aged ; Atrophy ; genetics ; Basal Ganglia Diseases ; diagnosis ; genetics ; DNA Mutational Analysis ; Dentate Gyrus ; pathology ; Family Health ; Female ; Globus Pallidus ; pathology ; Humans ; Male ; Middle Aged ; Nerve Tissue Proteins ; genetics ; Pedigree ; Trinucleotide Repeat Expansion ; genetics ; Young Adult

OBJECTIVETo study the pattern of CGG repeat instability within germline cells derived from two male fetuses affected with Fragile X syndrome (FXS).

METHODSThe length and methylation status of CGG repeats within the testes of a fetus carrying a full FXS mutation and another fetus carrying mosaicism FXS mutation were analyzed with Southern blotting and AmplideX FMR1 PCR. Immunohistochemistry was also applied for the measurement of FMR1 protein (FMRP) expression within the testes.

RESULTSFor the fetus carrying the full mutation, Southern blotting analysis of the PCR product has detected an expected band representing the full mutation in its brain and a premutation band of > 160 CGG repeats in its testis. Whereas the pattern of premutation/full mutation in mosaic testis was similar to that in peripheral blood and no sign of contracted fragment was found other than a band of about 160 CGG repeats. Immunohistochemistry assay with a FMRP-specific antibody demonstrated a number of FMRP-positive germ cells, which suggested a contraction from full mutation to premutation alleles.

CONCLUSIONThis study has clarified the instability pattern of CGG repeat and expression of FMRP protein within the testes of fetuses affected with FXS, confirming that the CGG repeat can contract progressively within the germline. The FMRP expression in the testis is consistent with spermatogonium proliferation, and thus the contraction from full mutation to unmethylated premutations may occur for the requirement of FMRP expression during spermatogenesis. The better understanding of FMRP function during germ cell proliferation may elucidate the mechanism underlying the contraction of full FXS mutation in male germline.

Abortion, Eugenic ; Blotting, Southern ; Brain ; embryology ; metabolism ; DNA Methylation ; Fatal Outcome ; Fetus ; cytology ; metabolism ; Fragile X Mental Retardation Protein ; genetics ; metabolism ; Fragile X Syndrome ; diagnosis ; genetics ; Humans ; Immunohistochemistry ; Male ; Mosaicism ; Mutation ; Polymerase Chain Reaction ; Spermatozoa ; metabolism ; Testis ; cytology ; embryology ; metabolism ; Trinucleotide Repeat Expansion ; genetics

BACKGROUNDSpinocerebellar ataxias (SCAs) are a group of neurodegenerative disorders that primarily cause the degeneration in the cerebellum, spinal cord, and brainstem. We study the clinical characteristics, radiological features and gene mutation in Chinese families with SCAs.

METHODSIn this study, we investigated 10 SCAs Chinese families with SCA1, SCA3/Machado-Joseph disease (MJD), SCA7, SCA8. There were 27 people who were genetically diagnosed as SCA, of which 21 people showed clinical symptoms, and 6 people had no clinical phenotype that we called them presymptomatic patients. In addition, 3 people with cerebellar ataxia and cataracts were diagnosed according to the Harding diagnostic criteria but failed to be recognized as SCAs on genetic testing. Clinical characteristic analyses of each type of SCAs and radiological examinations were performed.

RESULTSWe found that SCA3/MJD was the most common subtype in Han population in China, and the ratio of the pontine tegmentum and the posterior fossa area was negatively correlated with the number of cytosine-adenine-guanine (CAG) repeats; the disease duration was positively correlated with the International Cooperative Ataxia Rating Scale score; and the CAG repeats number of abnormal alleles was negatively correlated with the age of onset.

CONCLUSIONSCollectively our study is a systematic research on SCAs in China, which may help for the clinical diagnosis and prenatal screening of this disease, and it may also aid toward better understanding of this disease.

Adult ; DNA Repeat Expansion ; genetics ; Female ; Humans ; Machado-Joseph Disease ; genetics ; pathology ; Male ; Mutation ; genetics ; Spinocerebellar Ataxias ; genetics ; pathology ; Trinucleotide Repeat Expansion ; genetics

OBJECTIVETo analyze the clinical and genetic features of a family with Parkinson's disease caused by expansion of CAG triplet repeat in the ATXN2 gene.

METHODSThe CAG/CAA repeat in the ATXN2 gene was analyzed by polymerase chain reaction (PCR) and Sanger sequencing.

RESULTSMolecular testing has documented a pathological heterozygous expansion of the CAG repeat from 33 to 35 in 6 patients and other 8 family members. Two patients had pure CAG triplet repeat expansion in their ATXN2 gene, while others had CAA interruption.

CONCLUSIONExpanded CAG/CAA repeat in the ATXN2 gene is the causative mutation of the disease in this family.The 8 members with expanded CAG/CAA repeat may be asymptomatic patients. It is supposed that the number and configuration of the ATXN2 CAG/CAA repeat expansion may play an important role in the phenotypic variability of Parkinson's disease.

Aged ; Ataxin-2 ; genetics ; Base Sequence ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; Parkinson Disease ; genetics ; pathology ; Pedigree ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; methods ; Trinucleotide Repeat Expansion ; genetics

OBJECTIVETo screen for potential mutations of androgen receptor (AR) gene in a patient clinically diagnosed as Kennedy disease.

METHODSPolyglutamine expansion (PQE) induced by a duplication of CAG trinucleotide tandem-repeat in exon 1 of the AR gene was detected with PCR and T-clone sequencing.

RESULTSCompared with the number of CAG repeat of 22 in the normal allele, the number of CAG repeats has increased to 45 in the mutant allele carried by the patient. This has fit with the diagnostic criteria for Kennedy disease.

CONCLUSIONA mutation of PQE has been detected in the patient with Kennedy disease. Detection of PQE in AR gene can be used as reliable method to identify the Kennedy disease.

Base Sequence ; Bulbo-Spinal Atrophy, X-Linked ; blood ; diagnosis ; genetics ; Creatine Kinase ; blood ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Receptors, Androgen ; genetics ; Trinucleotide Repeat Expansion

OBJECTIVETo report on a Chinese family from Wenzhou with genetically confirmed Kennedy disease and describe its clinical and genetic features.

METHODSThe clinical phenotype and the level of relevant biochemical markers were assessed. To determine the number of CAG repeats in the exon 1 of androgen receptor (AR) gene, genomic DNA was extracted from peripheral blood samples of the family members, amplified by PCR and identified by DNA sequencing.

RESULTSThe proband showed predominantly proximal limb weakness, fasciculation, muscle atrophy, gynecomastia, sexual dysfunction and increased serum creatine kinase. Myopathy and neuropathy were identified by electromyography. Two other affected males and 2 affected female carriers were identified to carry an expanded CAG repeat in the AR gene. The numbers of CAG repeats were found to be 43 in the proband, 43 and 42 in the other two affected males, one of which had similar clinical symptoms to the proband.

CONCLUSIONThe family was diagnosed with Kennedy disease by analysis of the AR gene.

Adolescent ; Adult ; Base Sequence ; Bulbo-Spinal Atrophy, X-Linked ; blood ; diagnosis ; genetics ; Creatine Kinase ; blood ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Pedigree ; Receptors, Androgen ; genetics ; Trinucleotide Repeat Expansion ; Young Adult

Hereditary spinocerebellar ataxia type 17 (SCA17) is an autosomal dominantly inherited progressive degenerative disease of the nervous system. Also known as Huntington's disease-like 4(HDL4), SCA17 mainly features ataxia, muscle dystonia and psychiatric symptoms. The gene predisposing to SCA17 has been mapped and cloned, which encodes a TATA-binding protein (TBP). A CAG repeat expansion in the coding region of TBP gene can cause polyglutamine chain extension in the protein. This paper reviews recent progress in the research on SCA17 in regard to its clinical, etiology, pathology and pathogenesis.
Animals ; Humans ; Huntington Disease ; genetics ; pathology ; Spinocerebellar Ataxias ; genetics ; pathology ; TATA-Box Binding Protein ; genetics ; Trinucleotide Repeat Expansion

OBJECTIVETo compare the distribution of (CAG)n and (GGN)n repeats polymorphisms of androgen receptor (AR) gene between Hui and Han ethnic Chinese from Ningxia.

METHODSGenotypes of above repeats were determined with DNA sequencing method.

RESULTSThe distribution of (GGN)n repeats was significantly different between the two ethnic groups (P< 0.01), though no such difference was detected with (CAG)n repeats (P> 0.05). Particularly, Han Chinese women carrying 23 GGN repeats were significantly fewer (48.4%) than Hui women (64.7%, P=0.01).

CONCLUSIONThe distribution of GGN repeat is significantly differently among Hui and Han Chinese ethnics from Ningxia.

Alleles ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; ethnology ; Female ; Genotype ; Humans ; Male ; Molecular Sequence Data ; Polymorphism, Genetic ; Population Groups ; genetics ; Receptors, Androgen ; genetics ; Trinucleotide Repeat Expansion ; Trinucleotide Repeats