Prenatal diagnosis and molecular cytogenetic characterization of chromosome 22q11.2 deletion syndrome associated with congenital heart defects

ObjectiveTo report prenatal diagnosis of 22q11.2 deletion syndrome in a pregnancy with congenital heart defects in the fetus.Case reportA 26-year-old, primigravid woman was referred for counseling at 24 weeks of gestation because of abnormal ultrasound findings of fetal congenital heart defects. The Level II ultrasound revealed a singleton fetus with heart defects including overriding aorta, small pulmonary artery, and ventricular septal defect. Cordocentesis was performed. The DNA extracted from the cord blood was analyzed by multiplex ligation-dependent amplification (MLPA). The MLPA showed deletion in the DiGeorge syndrome (DGS) critical region of chromosome 22 low copy number repeat (LCR) 22-A∼C. Conventional cytogenetic analysis revealed a normal male karyotype. Repeated amniocentesis and cordocentesis were performed. Whole-genome array comparative genomic hybridization (aCGH) on cord blood was performed. aCGH detected a 3.07-Mb deletion at 22q11.21. Conventional cytogenetic analysis of cultured amniocytes revealed a karyotype 46,XY. Metaphase fluorescence in situ hybridization (FISH) analysis on cultured amniocytes confirmed an interstitial 22q11.2 deletion.ConclusionPrenatal ultrasound findings of congenital heart defects indicate that the fetuses are at increased risk for chromosome abnormalities. Studies for 22q11.2 deletion syndrome should be considered adjunct to conventional karyotyping. Although FISH has become a standard procedure for diagnosis of 22q11.2 deletion syndrome, MLPA can potentially diagnose a broader spectrum of abnormalities, and aCGH analysis has the advantage of refining the 22q11.2 deletion breakpoints and detecting uncharacterized chromosome rearrangements or genomic imbalances.     

Molecular cytogenetic characterization of de novo concomitant proximal 21q deletion of 21q11.2q21.3 and distal Xp deletion of Xp22.33p22.2 due to an unbalanced X;21 translocation detected by amniocentesis

ObjectiveWe present molecular cytogenetic characterization of de novo concomitant proximal 21q deletion of 21q11.2q21.3 and distal Xp deletion of Xp22.33p22.2 due to an unbalanced X; 21 translocation detected by amniocentesis.Case reportA 35-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X,der(X)t(X; 21) (p22.2; q21.3),-21. Simultaneous array comparative genomic hybridization (aCGH) revealed the result of an 11.9-Mb Xp22.33p22.2 deletion encompassing HCCS, SHOX, AMELX and OFD1 and a 15.4-Mb 21q11.2q21.3 deletion encompassing NRIP1 and APP. The pregnancy was subsequently terminated, and a malformed fetus was delivered with craniofacial dysmorphism. The parental karyotypes were normal. Polymorphic DNA marker analysis by quantitative fluorescence polymerase chain reaction (QF-PCR) confirmed a paternal origin of the 21q proximal deletion. Cytogenetic analysis of cord blood confirmed the karyotype of 45,X,der(X)t(X; 21) (p22.2; q21.3),-21. aCGH analysis of the cord blood confirmed the prenatal diagnosis.ConclusionQF-PCR analysis is useful for determination of the parental origin of a de novo unbalanced X; autosome translocation detected by prenatal diagnosis. The information acquired is useful for genetic counseling under such a circumstance.     

Prenatal features of 17q12 microdeletion and microduplication syndromes: A retrospective case series

ObjectiveTo present the experience on prenatal features of 17q12 microdeletion and microduplication syndromes.Materials and methodsPrenatal chromosomal microarray analysis (CMA) were conducted between January 2015 and December 2018 at a single Chinese tertiary medical centre. Information of cases identified with 17q12 microdeletion or microduplication syndromes were retrospectively collected. Foetal ultrasonographic findings were reviewed, and other information about the gestation week at diagnosis, inheritance and pregnancy outcomes were also included.ResultsTen pregnancies with 17q12 microdeletion and 4 with 17q12 microduplication were identified. The copy number variation (CNV) sizes were 1.39–1.94 Mb in the deleted cases and 1.42–1.48 Mb in the duplicated cases, respectively. All the duplicated and deleted regions included HNF1B and LHX1 genes. Most individuals with 17q12 deletion presented kidney anomalies (9/10), with renal hyperechogenicity being the most common finding (7/10). Fetuses with 17q12 duplication presented a wide phenotypic spectrum, including “double bubble” sign, structural anomalies of the heart and growth anomalies.ConclusionsOur experience further demonstrated the high correlation between 17q12 microdeletion and renal anomalies especially hyperechogenic kidneys. Structural anomalies of the heart were newly identified phenotypes of 17q12 duplication during prenatal period. Besides, growth anomalies and duodenal atresia might be associated with the duplication.     

Prenatal diagnosis of familial 22q11.2 deletion syndrome in a pregnancy with concomitant cardiac and urinary tract abnormalities in the fetus and the mother

ObjectiveWe present prenatal diagnosis of familial 22q11.2 deletion syndrome in a pregnancy with concomitant cardiac and urinary tract abnormalities in the fetus and the mother.Case reportA 28-year-old woman primigravid underwent amniocentesis at 23 weeks of gestation because of fetal ultrasound findings of aortic stenosis, interrupted aortic arch (IAA), left multicystic kidney, right hydronephrosis and ureterocele. Amniocentesis revealed a karyotype of 46,XX. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 22q11.21 (18,894,835-21,505,417) × 1.0 [GRCh37 (hg19)] with a 2.611-Mb 22q11.21 deletion encompassing 41 Online Mendelian Inheritance in Man (OMIM) genes including UFD1L, TBX1, GNB1L, COMT and MED15. aCGH analysis on the DNAs extracted from parental bloods confirmed that the mother carried the same 22q11.21 microdeletion. Level II ultrasound additionally found ventricular septal defect (VSD) and persistent left superior vena cava (PLSVC). Examination of the woman showed short stature, malar hypoplasia, hypertelorism, bulbous nasal tip, prominent nasal root, hypoplasia of nasal wings, right renal agenesis, left ureterovesical reflux and VSD with repair, but normal intelligence and normal neuropsychiatric development. The woman decided to continue the pregnancy, and a 2903-g female baby was delivered at 38 weeks of gestation with left multicystic kidney, right hydronephrosis, dysgenesis of corpus callosum, IAA, VSD, PLSVC, patent ductus arteriosus, patent foramen ovale, atrial septal defect, dilated main pulmonary artery and tricuspid regurgitation. The neonate died at the age of one month.ConclusionPrenatal diagnosis of concomitant congenital heart defects and urinary tract abnormalities in the fetus and the parent should raise a suspicion of familial 22q11.2 deletion syndrome.     

Prenatal diagnosis and molecular cytogenetic characterization of a 1.07-Mb microdeletion at 5q35.2–q35.3 associated with NSD1 haploinsufficiency and Sotos syndrome

ObjectiveTo present prenatal diagnosis and molecular cytogenetic characterization of a de novo 5q35 microdeletion associated with Sotos syndrome.MethodsThis was the first pregnancy of a 29-year-old woman. The pregnancy was uneventful until 27 weeks of gestation when left ventriculomegaly was first noted. At 31 weeks of gestation, polyhydramnios, macrocephaly, and ventriculomegaly were prominent on ultrasound, and left pyelectasis and bilateral ventriculomegaly were diagnosed on magnetic resonance imaging. The woman underwent amniocentesis and cordocentesis at 32 weeks of gestation. Conventional cytogenetic analysis was performed using cultured amniocytes and cord blood lymphocytes. Array comparative genomic hybridization (aCGH) was performed on uncultured amniocytes and parental blood. Metaphase fluorescence in situ hybridization (FISH) was performed on cultured lymphocytes.ResultsConventional cytogenetics revealed a karyotype of 46,XX. aCGH on uncultured amniocytes revealed a de novo 1.07-Mb microdeletion at 5q35.2–q35.3 encompassing NSD1. Metaphase FISH analysis on the cord blood lymphocytes confirmed the deletion at 5q35.2. The postnatal phenotype was consistent with Sotos syndrome.ConclusionFetuses with Sotos syndrome may present macrocephaly, polyhydramnios, ventriculomegaly, and pyelectasis in the third trimester. aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome.     

Prenatal diagnosis of aneuploidy and deletion 22q11.2 in fetuses with ultrasound detection of cardiac defects

OBJECTIVE: We report a prospective database evaluation of the occurrence of aneuploidy and deletion 22q11.2 after prenatal detection of cardiac abnormalities. To ensure the maximum inclusion, all cardiac defects were considered, with the exception of echogenic intracardiac foci. STUDY DESIGN: Prenatal specimens with ultrasound findings of cardiac defects were identified. Physicians were provided supplementary information that described the risk of deletion 22q11.2 syndrome if the karyotype was normal. On approval, fluorescence in situ hybridization was performed to identify the 22q11.2 microdeletion. RESULTS: Prenatal detection of cardiac abnormalities identified aneuploidy or unbalanced chromosome rearrangements in 41% of the cases that were studied. In those fetuses with normal karyotypes, 3% had the deletion 22q11.2. CONCLUSION: These results indicate that prenatal ultrasound findings of congenital heart defects identify fetuses who are at increased risk for chromosome abnormalities. Fetuses with normal karyotypes should consider having fluorescence in situ hybridization studies for the microdeletion 22q11.2 syndrome. Chromosome and fluorescence in situ hybridization studies of family members should be recommended when a fetus is identified as having the deletion 22q11.2.     

非梗阻性无精子症和隐匿精子症与睾丸体积、血FSH和AZF基因微缺失的相关性分析

目的：探讨非梗阻性无精子症和隐匿精子症与睾丸体积、血FSH和AZF基因微缺失的相关性。方法：161例男性不育患者分为非梗阻性无精子症（A组,n=86）、隐匿精子症（B组,n=49）、严重少精子症（c组,n=13）和其它患者（D组,n=13,包括死精子症4例,梗阻性无精子症3例,正常精子1例,其他少弱精子症5例）,进行睾丸体积、血FSH水平和彳砑基因微缺失检测,AZF基因微缺失检测位点包括AZFa（sY84、sY86）、AZFb（sYl27、sYl34）、AZFcd（sY254、sY255、sYl57、sYl45和sYl52）。结果：4组睾丸体积〈12ml的比例分别为73．26％（63／86）、34．69％（17／49）、7．69％（1／13）、30．77％（4／13）;4组FSH水平升高1倍以上的比例分别为67．44％（58／86）、32．65％（16／49）、15．38％（2／13）和O．OO％（o／13）,组间均有极显著统计学差异（P〈O．001）;4组4ZF基因微缺失率分别为15．12％（13／86）．18．37％（9／49）、0．oo％（o／13）和0．00％（0／13）,组间均无统计学差异（P〉0．05）,其中A组爿zn基因缺失1例,AZF（b＋c＋d）缺失5例,AZF（c＋d）基因缺失7例,B组9例均AZFC和（或MZFd基因缺失,c组和D组均未见AZF基因缺失。结论：随着生精功能障碍程度的加重,血FSH水平升高和睾丸体积缩小趋势明显,而与AZF缺失几率无高度相关性;但在非梗阻性无精子症和隐匿精子症组中AZF基因缺失几率仍然偏高,AZFa和AZFb缺失大多出现在非梗阻性无精子症组中,而隐匿精子症组以AZFc和AZFd缺失为主。     

Detection of recurrent transmission of 17q12 microdeletion by array comparative genomic hybridization in a fetus with prenatally diagnosed hydronephrosis,hydroureter, and multicystic kidney,and variable clinical spectrum in the family

ObjectiveThis study was aimed at detection of recurrent transmission of the 17q12 microdeletion in a fetus with congenital anomalies of the kidney and urinary tract.Materials and MethodsA 35-year-old woman was referred to the hospital at 20 weeks' gestation because of hydronephrosis in the fetus. The mother was normal and healthy. Her second child was a girl who had bilateral dysplastic kidneys that required hemodialysis, and died at the age of 5 years. During this pregnancy, the woman underwent amniocentesis at 18 weeks' gestation because of advanced maternal age. Cytogenetic analysis revealed a karyotype of 46,XY. Prenatal ultrasound showed left hydronephrosis with a tortuous ureter, right hydronephrosis, and increased echogenicity of the kidneys. Fetal magnetic resonance imaging showed right dilated renal calyces, left hydronephrosis, hydroureter, and multicystic kidney. The pregnancy was subsequently terminated. Array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization were applied for genetic analysis using umbilical cord, maternal blood, and cultured amniocytes.ResultsaCGH analysis on umbilical cord detected a 1.75-Mb deletion at 17q12 including haploinsufficiency of LHX1 and HNF1B. aCGH analysis on maternal blood detected a 1.54-Mb deletion at 17q12 including haploinsufficiency of LHX1 and HNF1B. Metaphase fluorescence in situ hybridization analysis on cultured amniocytes and maternal blood lymphocytes using 17q12-specific bacterial artificial chromosome probe showed 17q12 microdeletion in the fetus and the mother.ConclusionPrenatal diagnosis of recurrent renal and urinary tract abnormalities in the fetus should include a differential diagnosis of familial 17q12 microdeletion.     

Prenatal diagnosis of a familial normal euchromatic variant of dup(15)(q11.2q11.2) in a pregnancy with a favorable outcome

ObjectiveWe present prenatal diagnosis of a familial normal euchromatic variant of dup(15)(q11.2q11.2) in a pregnancy with a favorable outcome.Case reportA 32-year-old woman underwent elective amniocentesis at 17 weeks of gestation because of anxiety. Amniocentesis revealed a karyotype of 46,XX,dup(15)(q11.2q11.2). Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1–22, X) × 2 with no genomic imbalance. Cytogenetic analysis of the parental bloods showed that the mother had a karyotype of 46,XX,dup(15)(q11.2q11.2), and the father had a karyotype of 46,XY. Prenatal ultrasound findings were unremarkable. A healthy 2948 g female baby was delivered at 39 weeks of gestation without any phenotypic abnormality. Cytogenetic analysis of the cord blood revealed a karyotype of 46,XX,dup(15)(q11.2q11.2).ConclusionPrenatal diagnosis of dup(15)(q11.2q11.2) should include a differential diagnosis of a 15q11.2 (BP1-BP2) microduplication encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1, and aCGH analysis is useful for the differential diagnosis under such a circumstance.     

A 1.37-Mb 12p11.22–p11.21 deletion coincident with a 367-kb 22q11.2 duplication detected by array comparative genomic hybridization in an adolescent girl with autism and difficulty in self-care of menstruation

ObjectiveTo present an array comparative genomic hybridization (aCGH) characterization of a 12p11.22–p11.21 microdeletion and 22q11.2 microduplication in an adolescent girl with autism, mental retardation, facial dysmorphism, microcephaly, behavior problems, and an apparently balanced reciprocal translocation of t(8;12)(q24.3;p11.2).Materials and methodsA 13-year-old girl was referred to the hospital because of autism, mental retardation, and difficulty in the self-care of her menstruation. Cytogenetic analysis revealed an apparently balanced reciprocal translocation and a karyotype of 46,XX,t(8;12) (q24.3;p11.2)dn. The girl manifested microcephaly, hypertelorism, flat facial profile, prominent forehead, thick scalp hair, upslanting palpebral fissures, broad nasal bridge, bulbous nose, right simian crease, bilateral clinodactyly of the fifth fingers, bilateral pes cavus, learning difficulties, mental retardation, emotional instability, cognitive impairment, behavior problems, jumping-like gaits, and autistic spectrum disorder. aCGH was performed to evaluate genomic imbalance in this patient.ResultsaCGH analysis revealed a 1.37-Mb 12p11.22–p11.21 microdeletion or arr [hg 19] 12p11.22-p11.21 (30,645,008–32,014,774) × 1 and a 367-kb 22q11.21 microduplication or arr [hg 19] 22q11.21 (18,657,470–19,024,306) × 3. The 1.37-Mb 12p11.22–p11.21 microdeletion encompassed 26 genes including IPO8, CAPRIN2, and DDX11, and the 367-kb 22q11.21 microduplication encompassed 20 genes including USP18, DGCR6, PRODH, and DGCR2.ConclusionAn apparently balanced translocation may be in fact affected by concurrent deletion and duplication in two different chromosomal regions. Our presentation provides information on diagnostic phenotype of 12p11.22–p11.21 microdeletion and 22q11.2 microduplication.     

Microdeletion 22q11.2, Kousseff syndrome and spina bifida

A fetus was diagnosed on ultrasound scan as having sacral spina bifida and a ventricular septal defect in the heart. At postmortem examination the cardiac defect was found to be a conotruncal abnormality, and there was a cleft palate, some facial dysmorphism as well as the spina bifida. A diagnosis of Kousseff syndrome was made, but detailed cytogenetics subsequently revealed a 22q11.2 deletion. In the light of these findings, and on review of the literature, we suggest that spina bifida is recognized as a feature of the variable phenotype associated with this microdeletion.     

Y chromosome microdeletions in infertile men: prevalence, phenotypes and screening markers for the Indian population

Purpose

Yq microdeletions are the leading genetic cause of male infertility and its detection is clinically relevant for appropriate genetic counseling. We aimed to determine the prevalence and type of Yq microdeletions, the associated seminal phenotypes and the STS markers that are relevant for its testing in Indian population.

Methods

Yq microdeletion analysis was carried out in 1,636 infertile cases in our centers. Additional data was collected from published studies in Indian population leading to a total of 3,647 cases.

Results

In our cohort, 3.4 % (56/1,636) of infertile men had Yq microdeletions. Combining the data from other published studies identified 215/3,647 (5.8 %) infertile individuals to harbor Yq microdeletions; with 6.4 % in azoopsermia, 5.8 % in oligozoospermia and 3.2 % in oligoasthenozoospermia and teratozoospermia cases. No significant differences in the deletion frequencies were observed between idiopathic vs non idiopathic cases (5.8 vs 8.6 % respectively). Deletions of AZFc were at highest frequency (46.6 %) with double deletions most commonly observed in azoospermic subjects. With respect to the STS markers, screening with the six European Academy of Andrology (EAA) markers would miss 3.1 % of cases; additional non EAA markers that would contribute significantly to screening are sY746, sY82, sY121, sY128, sY130, sY143, sY145 & sY160.

Interpretations and conclusions

The frequency of Yq microdeletions is lower in Indian population as compared to Western counterparts. There is no major association of Yq microdeletions with seminal parameters or cause of infertility. Clinically it will be necessary to offer Yq microdeletion testing to all the classes of infertile men. The EAA markers may not be adequate to detect microdeletions in Indian infertile men.     

Prenatal diagnosis and molecular cytogenetic characterization of a chromosome 15q24 microdeletion

ObjectiveWe present prenatal diagnosis, molecular cytogenetic characterization and genetic counseling of a chromosome 15q24 microdeletion of paternal origin.Case reportA 34-year-old primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. Simultaneous array comparative genomic hybridization (aCGH) analysis on amniotic fluid revealed a de novo 2.571-Mb microdeletion of 15q24.1-q24.2. Prenatal ultrasound findings were unremarkable except persistent left superior vena cava and enlarged coronary sinus. The woman requested repeat amniocentesis at 22 weeks of gestation, and aCGH analysis confirmed the result of arr 15q24.1q24.2 (72,963,970–75,535,330) × 1.0 [GRCh37 (hg19)] and a 15q24 microdeletion encompassing the genes of STRA6, CYP11A1, SEMA7A, ARID3B, CYP1A1, CYP1A2, CSK and CPLX3. The parents did not have such a deletion, and polymorphic DNA marker analysis confirmed a paternal origin of the de novo deletion. Metaphase fluorescence in situ hybridization analysis confirmed a 15q24 deletion. The parents elected to terminate the pregnancy, and a malformed fetus was delivered with characteristic facial dysmorphism.ConclusionSimultaneous aCGH analysis of uncultured amniocytes at amniocentesis may help to detect rare de novo microdeletion disorders.     

Prenatal diagnosis of a familial 15q11.2 (BP1-BP2) microdeletion encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in a fetus with ventriculomegaly,microcephaly and intrauterine growth restriction on prenatal ultrasound

Objective

We present prenatal diagnosis of a 15q11.2 (BP1-BP2) microdeletion encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in a fetus with ventriculomegaly, microcephaly and intrauterine growth restriction (IUGR) on prenatal ultrasound.

Prenatally diagnosed 17q12 microdeletion syndrome with a novel association with congenital diaphragmatic hernia

We describe the first reported case of a prenatally diagnosed and recently described 17q12 microdeletion syndrome. The fetus was noted to have a congenital diaphragmatic hernia (CDH), echogenic kidneys and cystic left lung on prenatal ultrasound. The patient underwent amniocentesis which resulted in a normal fluorescence in-situ hybridization and karyotype. An oligonucleotide microarray was then performed which demonstrated a 1.4-Mb deletion within the 17q12 region. The deletion caused haploinsufficiency for 17 genes, including AATF, ACACA, DDX52, DUSP14, GGNBP2, HNF-1B, LHX1, PIGW, SYNRG, TADA2A, and ZNHIT3. The deleted region on 17q12 is similar in size and gene content to previously reported 17q12 microdeletion syndromes, which have a minimal critical region of 1.52 Mb. The newly described 17q12 microdeletion syndrome has been associated with MODY5 (maturity-onset of diabetes of the young type 5), cystic renal disease, pancreatic atrophy, liver abnormalities, cognitive impairment and structural brain abnormalities. CDH has not been previously described with the 17q12 microdeletion syndrome. We hypothesize that CDH is part of the spectrum of this syndrome and likely not detected postnatally due to high prenatal mortality.     

Cytogenetic and Y chromosome microdeletion screening studies in infertile males with Oligozoospermia and Azoospermia in Southeast Turkey

Purpose

In view of the genetic risks for the next generation, the importance of careful evaluation of karyotypes and AZF microdeletions in male infertility prior to assisted reproduction is evident. In the present study, it is aimed to investigate the frequency and types of both major chromosomal abnormalities by using standard cytogenetic methods and Y chromosome microdeletions of infertile males with azoospermia and oligozoospermia to give appropriate genetic counseling before assisted reproduction techniques in southeast Turkey.

Methods

A total of 80 infertile males (52 were azoospermic, 25 oligospermic and 3 asthenospermic) were studied for the cytogenetic evaluation and molecular AZF screening program prior to use of assisted reproduction techniques. A detailed history was taken for each man. Karyotyping was performed on peripheral blood lymphocytes according to standard methods. Polymerase chain reaction (PCR) amplification by using 15 Y-specific sequence-tagged sites of AZF region was performed to screen the microdeletions in the AZF region of Y chromosome.

Results

Of 80 cases, 71 had normal karyotype (46,XY). The total prevalence of chromosomal abnormalities was found to be 11.2% (9/80), including seven patients with Klinefelter syndromes and two patients with balanced autosomal rearrangements. All of the patients with Klinefelter Syndrome had azoospermia, but carriers with translocation had oligospermia. The deletions of Y chromosome were seen in one patient (1.3%) with features of normal karyotype and azoospermia. Microdeletions were seen in the AZFc and AZFd regions. Neither AZFa nor AZFb microdeletions were detected.

Conclusions

The occurrence of chromosomal anomalies and Y chromosome microdeletions among infertile males strongly suggests the need for routine genetic testing and counseling prior to employment of assisted reproduction techniques.     

Mosaicism for a 15q11.2 microduplication with a normal euploid cell line at amniocentesis in a pregnancy with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the microduplication

ObjectiveWe present mosaicism for a 15q11.2 microduplication with a normal euploid cell line at amniocentesis in a pregnancy with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the microduplication.Case reportA 35-year-old, primigravid woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed 33.76% mosaicism for a 15q11.2 microduplication. She was referred for genetic counseling. Repeat amniocentesis was performed at 23 weeks of gestation, and the karyotype was 46,XY. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed the result of arr [GRCh37 (hg19)] 15q11.2 (23, 889, 686–25,514,125) × 2.45, consistent with a mosaic 1.624-Mb microduplication with the mosaic level of 40%–45% (log₂ ratio = 0.28) encompassing nine OMIM genes of MAGEL2, NDN, PWRN2, PWRN1, NPAP1, SNRPN, SNHG14, SNORD116-1 and SNORD115-1. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes detected a 15q11.2 duplication in 19 cells, consistent with 19% (19/100 cells) mosaic15q11.2 duplication. Polymorphic DNA marker analysis excluded uniparental disomy (UPD) 15. Prenatal ultrasound findings were unremarkable. She was advised to continue the pregnancy, and a 3865-g phenotypically normal male baby was delivered. aCGH analysis on the DNA extracted from cord blood at birth and buccal mucosal cells at age four months revealed arr (1–22) × 2, X × 1, Y × 1 and detected no genomic imbalance in all samples. Interphase FISH analysis on 104 buccal mucosal cells at age four months detected four cells (4/104 = 4%) with a 15q11.2 duplication, compared with 0% (0/102 cells) in the normal control. The neonate was normal in the development.ConclusionMosaicism for a 15q11.2 microduplication at amniocentesis with a normal euploid cell line can be a benign condition and associated with a favorable fetal outcome and postnatal decrease of the aneuploid cell line with the microduplication.     

Prenatal diagnosis of partial monosomy 18p(18p11.2-->pter) and trisomy 21q(21q22.3-->qter) with alobar holoprosencephaly and premaxillary agenesis

A prenatal diagnosis of partial monosomy 18p(18p11.2-->pter) and trisomy 21q(21q22.3-->qter) in a fetus with alobar holoprosencephaly (HPE) and premaxillary agenesis (PMA) but without the classical Down syndrome phenotype is reported. A 27-year-old primigravida woman was referred for genetic counselling at 21 weeks' gestation due to sonographic findings of craniofacial abnormalities. Level II ultrasonograms manifested alobar HPE and median orofacial cleft. Cytogenetic analysis and fluorescence in situ hybridization (FISH) on cells obtained from amniocentesis revealed partial monosomy 18p and a cryptic duplication of 21q,46,XY,der(18)t(18;21)(p11.2;q22.3), resulting from a maternal t(18;21) reciprocal translocation. The breakpoints were ascertained by molecular genetic analysis. The pregnancy was terminated. Autopsy showed alobar HPE with PMA, pituitary dysplasia, clinodactyly and classical 18p deletion phenotype but without the presence of major typical phenotypic features of Down syndrome. The phenotype of this antenatally diagnosed case is compared with those observed in six previously reported cases with monosomy 18p due to 18;21 translocation. The present study is the first report of concomitant deletion of HPE critical region of chromosome 18p11.3 and cryptic duplication of a small segment of distal chromosome 21q22.3 outside Down syndrome critical region. The present study shows that cytogenetic analyses are important in detecting chromosomal aberrations in pregnancies with prenatally detected craniofacial abnormalities, and adjunctive molecular investigations are useful in elucidating the genetic pathogenesis of dysmorphism.     

Familial transmission of recurrent 15q11.2 (BP1-BP2) microdeletion encompassing NIPA1, NIPA2, CYFIP1, and TUBGCP5 associated with phenotypic variability in developmental,speech, and motor delay

Objective

We present recurrent 15q11.2 (BP1-BP2) microdeletion encompassing NIPA1, NIPA2, CYFIP1, and TUBGCP5 in a family with phenotypic variability in developmental, speech, and motor delay.

Y chromosome microdeletions and male infertility

Classical cytogenetic mapping has identified a locus on the long arm of the human Y chromosome that is required for spermatogenesis and is termed AZF, an acronym for the hypothetical azoospermia factor encoded by this locus. Recent molecular attempts to identify the gene corresponding to this locus have revealed that there are at least three genes in three separate microdeletion intervals. Two of these microdeletion intervals contain genes encoding proteins with potential roles in RNA metabolism. These genes are members of Y-encoded gene families with autosomal homologues. The cell biology of one of these genes, RBM (an acronym of RNA binding motif), is complex and suggests a role in pre-mRNA splicing.