Prenatal diagnosis of Jacobsen syndrome: analysis of four cases / 中华围产医学杂志

Objective To investiget the value of chromosome microarray analysis (CMA) in prenatal diagnosis of Jacobsen syndrome.Methods Among all gravidas who received karyotype analysis and CMA because of fetal congenital cardiac abnormalities in Shenzhen Maternity & Child Healthcare Hospital Affiliated to Southern Medical University from 2014 to 2016,four were diagnosed with fetal Jacobsen syndrome and enrolled in this study.Three amniotic fluid and one fetal tissue samples were collected.Peripheral blood specimens were collected from parents of these fetuses.Amniotic fluid samples and peripheral blood specimens were analyzed by karyotype analysis.CMA was performed to analyze amniotic fluid and fetal tissue samples.Multiplex ligation-dependent probe amplification was used to verify abnormal results revealed by CMA.Results (1) Prenatal ultrasound results:Fetus 1 was complicated with monocardian and transposition of the great arteries,fetus 2 with single umbilical artery and double superior vena cava,fetus 3 with severe constricted aorta and ventricular septal defect and fetus 4 with hypoplastic left heart syndrome and presented with a nuchal translucency of 0.27 cm.(2) Karyotyping results of the three amniotic fluid samples were 46,XY,del(11)(q23.3),46,XX,del(11)(q23.3) and 46,XX,del(11)(q23),respectively.(3) CMA results of the four fetuses were arr[GRCh37]11q24.1q25(121 872 273-134 934 196)× 1(13.062 Mb),arr[GRCh37]11q24.1q25(121 325 694-134 937 416)× 1 (13.611 Mb),arr[GRCh37]11q23.3q25(118 977 029-134 937 416)× 1 (15.960 Mb) and arr[GRCh37]11q24.1q24.3(123 144 040-130 308 335)× 1(7.164 Mb),respectively.All chromosomal aberrations in these fetuses were de novo as no abnormalities were found in their parents through karyotyping.All abnormal CMA results were confirmed by multiplex ligation-dependent probe amplification.Conclusions Jacobsen syndrome should be considered when fetuses are diagnosed with congenital cardiac abnormalities by ultrasound.CMA can be used to accurately diagnose Jacobsen syndrome and determine the region and size of chromosome deletion.

Combined G-banded karyotyping and multiplex ligation-dependent probe amplification for the detection of chromosomal abnormalities in fetuses with congenital heart defects / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of G-banded karyotyping in combination with multiplex ligation-dependent probe amplification (MLPA) as a tool for the detection of chromosomal abnormalities in fetuses with congenital heart defects.</p><p><b>METHODS</b>The combined method was used to analyze 104 fetuses with heart malformations identified by ultrasonography. Abnormal findings were confirmed with chromosomal microarray analysis (CMA).</p><p><b>RESULTS</b>Nineteen (18%) fetuses were found to harbor chromosomal aberrations by G-banded karyotyping and MLPA. For 93 cases, CMA has detected abnormalities in 14 cases including 10 pathogenic copy number variations (CNVs) and 4 CNVs of uncertain significance (VOUS). MLPA was able to detect all of the pathogenic CNVs and 1 VOUS CNV.</p><p><b>CONCLUSION</b>Combined use of G-banded karyotyping and MLPA is a rapid, low-cost and effective method to detect chromosomal abnormalities in fetuses with various heart malformations.</p>

Genetic analysis and prenatal diagnosis of two Chinese families with split hand foot malformation / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify genomic aberrations underlying pathogenesis of split hand foot malformation (SHFM) in two Chinese families, and to provide genetic counseling and prenatal diagnosis for them.</p><p><b>METHODS</b>Two sets of peripheral blood and amniotic fluid samples were collected from the patients. One was processed with routine culture and karyotype analysis. For another set, DNA was extracted and analyzed with array-based comparative genomic hybridization (array-CGH).</p><p><b>RESULTS</b>Karyotype analysis of peripheral blood samples for both probands was normal. Karyotype analysis of the amniotic fluid from family 1 has found no abnormality. However, analysis of amniotic fluid samples from the second family showed del(7)(q21q22.1). By array-CGH analysis, both blood and amniotic fluid samples from the first family showed a 662.3 kb dup(10q24.31q24.32). Array-CGH analysis of the blood sample from the second family was normal, whilst analysis of amniotic fluid sample revealed a 19.97 Mb del(7q11.23q21.3).</p><p><b>CONCLUSION</b>Array-CGH features high resolution, high accuracy and rapid diagnosis for unbalanced chromosomal aberration. The dup(10q24.31q24.32) and 19.97 Mb del(7q11.23q21.3) have been the cause of SHFM in the two families. Genetic counseling and prenatal diagnosis have been provided for both families in order to prevent this birth defect.</p>

Application of array-CGH and MLPA for detection of 4 cryptic unbalanced translocations / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To use array comparative genomic hybridization (array-CGH) and multiplex ligation-dependent probe amplification (MLPA) to detect unbalanced rearrangements in 4 cases suspected to have chromosome disease but were undetected with conventional karyotype analysis, and to assess the applicability of array-CGH and MLPA for detection of unbalanced translocation.</p><p><b>METHODS</b>Genomic DNA was extracted with standard procedures. All cases were analyzed by array-CGH and subtelomeric MLPA.</p><p><b>RESULTS</b>All of the cases were identified to have unbalanced translocations by array-CGH analysis, among which 3 were consistent with subtelomeric MLPA analysis. For the remaining one, its chromosomal abnormality was not detected by MLPA as the imbalance has occurred outside of target regions.</p><p><b>CONCLUSION</b>Both array-CGH and MLPA techniques can complement conventional karyotyping for detecting unbalanced translocations. The combination features both high resolution and efficiency for clinical use.</p>

Mutation analysis of the androgen receptor gene in a complete androgen insensitivity syndrome family / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the mutation of the androgen receptor gene in a family with complete androgen insensitivity syndrome and to explore the pathogenicity of the mutation.</p><p><b>METHODS</b>PCR and DNA sequencing were performed to study the AR gene mutation; Mbo I restriction endonuclease was used to detect existence of the mutation in normal controls; conservation of the mutation site was analyzed by comparison of the sequence of amino acid among different species.</p><p><b>RESULTS</b>The DNA sequence of the three patients contained the same substitution of a single nucleotide on codon 681 GAG to GAT of exon 4, which located in the ligand binding domain of the AR receptor and led to substitution of glutamic acid to aspartic acid in the AR receptor. Their mother was heterozygote of E681D. E681D was not observed in the normal controls. The E681 site was extremely conservative in different species.</p><p><b>CONCLUSION</b>The E681D mutation of the AR gene is a novel mutation of leading to complete androgen insensitivity syndrome.</p>

Chromosome aberration in a full-term neonate with low birth weight using microarray comparative genomic hybridization / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the chromosome aberration in a full-term male neonate with low birth weight, and to explore the possible causes for growth retardation in intrauterine development for the neonate.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral leukocytes of the neonate. Detection of genomic DNA copy number gain and loss was performed using microarray comparative genomic hybridization. Chromosome karyotype was obtained from cultured lymphocytes for the neonate and his parents in order to identify the origin of chromosome aberration.</p><p><b>RESULTS</b>Gain of 10q25.2-->qter (22 Mb) was observed in the full-term neonate with low birth weight. In addition, one chromosomal region, 15q26.2-->qter (5 Mb) was lost. The karyotype of the neonate was 46, XY, -15, +der(15), t(10;15)(q25;q26)pat.</p><p><b>CONCLUSION</b>The full-term neonate with low birth weight had a partial trisomy of 10q25.2-->qter with a partial monosomy of 15q26.2-->qter, both of them may contribute to the growth retardation in intrauterine development for the neonate case.</p>