ABSTRACT: To characterize molecular and cytogenetic abnormalities in six 46, XX males, and to investigate the clinical manifestations and underlying mechanisms in such patients.
Clinical data of six XX male patients were collected. Karyotyping, multiple polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) were utilized to detect and locate the sex determining region (SRY) gene.
PCR and FISH showed that all patients were SRY-positive XX males. All patients have their SRY gene located at the tip of derivative X chromosomes, which have resulted from translocation between short arms of X and Y chromosomes. High resolution karyotyping at 550-750 band level has revealed that the translocation breakpoints were at Xp22.33 and Yp11.2 in three patients. In the remaining patients, the breakpoints were either at Xp22.32 and Yp11.31 or Xp22.31 and Yp11.2. The breakpoints at Xp22.32, Xp22.31 and Yp11.31 were rarely reported. Genotype-phenotype correlation analysis indicated that the clinical manifestations were age-specific. Four adult patients have come to clinical attention due to infertility, with typical features including azoospermia and testis dysgenesis, whereas poorly developed secondary sexual characteristics and short stature were main complaints of adolescence patients, and short stature was the sole symptom in a child patient.
Combined karyotyping, PCR and FISH are important for the analysis of XX males. Particularly, high resolution karyotyping is valuable for the refinement of chromosome breakpoints and detailed analysis of genotype-phenotype correlation.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 08/2012; 29(4):408-12.
ABSTRACT: To explore the clinical feature and genetic diagnosis for Smith-Magenis syndrome (SMS).
The clinical data, including craniofacial anomalies, physical and mental status were analyzed. Routine and high resolution G-banding was performed to analyze the karyotype of the patient and her parents, and array comparative genomic hybridization (array CGH) was used to detect small chromosome anomaly.
A-two-year old girl was sent to our clinic for mental retardation and cardiac malformation. Some sleep problems were reported by parents, including difficulties falling asleep, shortened sleep cycles. She also had some neurobehavioral symptoms including hyperactivity and self-injurious behaviors head-banging. She had distinctive craniofacial features including low hairline, frontal bossing, a broad face, broad nasal bridge, a tented upper lip, prognathism, low-set ears and high-vaulted arch. She had moderate mental retardation. Cardiac findings included ventricular septal defect, atrial septal defect, overriding aorta and pulmonary hypertension. Primary ventriculomegaly was seen in magnetic resonance imaging (MRI). Routine karyotype analysis showed a karyotype of 46, XX. However, high resolution karyotype analysis showed a suspected partial deletion of the short arm of chromosome 17. Array comparative genomic hybridization (array CGH) finely mapped the deletion to a 3.8 Mb region on 17p11.2. The molecular karyotype was then ascertained as 46, XX.arr17p11.2(16543655-20374751)×1dn. The parents had normal karyotypes.
Smith-Magenis syndrome is a multisystem disorder characterized by developmental delay and mental retardation, distinctive craniofacial features, sleep disturbance and behavioral problems. Array comparative genomic hybridization (array CGH) finely mapped the deletion on 17p11.2.
Zhonghua er ke za zhi. Chinese journal of pediatrics 03/2012; 50(3):227-30.
ABSTRACT: To determine the origin of aberrant chromosomes involving the short arm of chromosome 8 in two mentally retarded children, and to correlate the karyotype with abnormal phenotype.
Routine G-banding was performed to analyze the karyotypes of the two patients and their parents, and array comparative genomic hybridization (array CGH) was used for the first patient for fine mapping of the aberrant region.
The first patient presented with only mental retardation. The father had normal karyotype. The mother had an apparent insertion translocation involving chromosomes 8 and 3 [46, XX, inv ins (3; 8) (q25.3; p23.1p11.2)], the karyotype of the child was ascertained as 46, XX, der(3) inv ins (3; 8)(q25.3; p23.1p11.2). Array CGH finely mapped the duplication to 8p11.21-8p22, a 26.9 Mb region. The other patient presented with mental retardation, craniofacial defects, congenital heart disease and minor skeletal abnormality. The mother had normal karyotype. The father had an apparently balanced translocation involving chromosome 8p and 11q, the karyotype was 46, XY, t(8; 11)(p11.2; q25). The karyotype of the child was then ascertained as 46, XX, der(11)t(8; 11)(p11.2; q25).
These results suggested that partial trisomy 8p was primary cause for the phenotypic abnormalities of the two patients, whereas a mild phenotypic effect was observed in patient 1. Parental karyotype analysis could help define the aberrant type and recurrent risk evaluation. In contract to routine karyotype analysis, aberrant regions could be mapped by array CGH with higher resolution and accuracy.
Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 06/2011; 28(3):247-50.