Clinical, cytogenetic, and molecular analyses of prenatally diagnosed mosaic tetrasomy for distal chromosome 15q and review of the literature

OBJECTIVES: To present prenatally detected mosaic tetrasomy for distal chromosome 15q and a review of the literature. CLINICAL SUBJECT AND METHODS: Amniocentesis was performed at 17 weeks' gestation because of advanced maternal age. Cytogenetic analysis revealed mosaicism for an analphoid supernumerary marker chromosome (SMC). The parental karyotypes were normal. Fluorescence in situ hybridization (FISH) and polymorphic DNA marker analysis were applied to study the origin of the SMC. Level II ultrasound revealed gastric dilation. The pregnancy was terminated, and a malformed fetus was delivered with characteristic dysmorphism. Multiple samplings of fetal and extraembryonic tissues were performed to investigate the mosaicism. RESULTS: Initial amniocentesis revealed mos 47,XY,+ mar[20]/46,XY[1], and repeat amniocentesis revealed 47,XY,+ mar[28]/46,XY[8]. FISH and polymorphic DNA marker analysis determined an origin from the distal 15q and an inverted duplication of 15q25.3 --> qter for the SMC. Karyotype of the fetus was designated as 47,XY,+ ace i(15) (qter --> q25.3::q25.3 --> qter)/46,XY de novo. The levels of tetrasomy for distal 15q were 28/40 in cord blood, 13/40 in liver, 14/40 in lungs, 27/40 in skin, 0/40 in placenta, and 40/40 in umbilical cord. The placenta showed an equal biparental inheritance (1:1). The umbilical cord inherited one copy of a paternal allele and three copies of a maternal allele (1:3) at distal 15q. Diallelic patterns with dosage ratios (paternal allele: maternal allele) of 1:2.5 in amniocytes, 1:2.3 in amnion, 1:2.2 in cord blood, 1:2.1 in skin, 1:1.4 in liver, and 1:1.4 in lungs. A maternal origin of the mosaic SMC(15) was determined. CONCLUSIONS: A diagnosis of mosaic analphoid SMCs in amniocytes should alert mosaic mirror-image duplication of euchromatin from some distal chromosomal segment such as distal 15q or distal 13q, and a risk for fetal abnormalities. Fetuses with mosaic tetrasomy for distal 15q may be associated with fetoplacental chromosomal discrepancy. Postnatal samplings of umbilical cord, placenta and amniotic membrane may provide additional clues to the cytogenetic discrepancy between fetal and extraembryonic tissues in prenatally detected mosaic analphoid SMCs.     

AZFc deletion detected in a newborn with prenatally diagnosed Yq deletion

A case of prenatally diagnosed Yq deletion is described. Fluorescence in situ hybridisation (FISH) was used to identify the abnormal chromosome and to exclude mosaicism. Based on the cytogenetic result and the ultrasound investigation the pregnancy was continued. A newborn with normal male genitalia was delivered. Microdeletion analysis of the Yq showed the absence of the AZFc region. This type of deletion has been described as being associated with azoospermia or oligozoospermia with a progressive decrease of sperm number over time. Long-term andrological follow-up of the newborn will be necessary with eventual cryoconservation of sperm at early adulthood. The present report proposes that AZF analysis combined with FISH has an important role in accurate genetic counselling in sex chromosome anomalies.     

Terminal deletion of chromosome 15q26.1: case report and brief literature review.

Terminal deletions of chromosome 15q are rare events, with only six cases previously described. Here we describe a seventh case of a terminal deletion of the long arm of chromosome 15, with the present case exhibiting clinical features not previously described.     

Prenatal diagnosis of the distal 11q deletion and review of the literature

OBJECTIVES: To present the prenatal diagnosis of de novo distal 11q deletions and a review of the literature. CLINICAL SUBJECTS AND METHODS: A 31-year-old primigravid woman underwent amniocentesis at 20 weeks' gestation because of a maternal serum alpha-fetoprotein (MSAFP) level of 2.63 multiples of the median. Amniocentesis demonstrated a karyotype of 46,XY,del(11)(q24.2). The parental karyotypes were normal. Level II ultrasound revealed short femurs and humeri, and overlapping of the toes. Postnatally, the proband manifested additional findings of the characteristic facial dysmorphism and camptodactyly. A 38-year-old gravida 2, para 1, woman underwent amniocentesis at 18 weeks' gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XX,del(11)(q24.1). The parental karyotypes were normal. Level II ultrasound did not show fetal structural abnormalities. Postnatally, the proband manifested characteristic facial dysmorphism and camptodactyly. RESULTS: Of these two cases, genetic marker analysis determined the paternally derived distal deletions of chromosome 11q and the deletion breakpoints. A comparison of the present cases with the reported cases of prenatally diagnosed distal 11q deletion is made. CONCLUSION: The distal 11q deletion can be identified prenatally because of parental balanced translocations involving chromosome 11, previous-term infants with an unbalanced rearrangement, advanced parental age, sonographically detected fetal abnormalities and abnormal maternal serum screening. Fetuses with de novo distal 11q deletions may be associated with elevated MSAFP and abnormal sonographic findings of the digits and limbs in the second trimester.     

Interstitial deletion of 13q22-->q31: case report and review of the literature

In the present study we describe a patient with characteristic brachydactily, developmental delay and interstitial del 13q22-->q31. After the review of the literature, few cases sharing similar chromosomal deletions were found and they displayed little resemblance with our patient. We discuss the phenotype correlation among the deleted regions in such cases.     

Prenatal detection of deletion 6q13q15 in a complex karyotype

OBJECTIVES: Prenatal diagnosis of a pregnancy with elevated maternal serum alpha-fetoprotein identified a karyotype with a complex chromosomal rearrangement, a Robertsonian translocation and a 6q deletion involving bands q13q15. Sonography identified mild IUGR, polyhydramnios and micrognathia. The infant presented with multiple congenital anomalies, primarily limited to the head and neck, including hypertelorism, broad nose, micrognathia, cleft palate, microglossia and low-set ears with microtia. METHODS: Amniocytes of the fetus and blood of the patient and her parents were analyzed by cytogenetics and fluorescence in situ hybridization. RESULTS: The karyotype on the fetus was 45,XX,t(3;21;20)(p12;q11.2;p11.2), del(6)(q13q15),der(13;14) (q10;q10)mat. CONCLUSION: The 13;14 Robertsonian translocation was inherited from the mother and the three-way translocation appeared to be balanced. The patient had facial dysmorphology similar to that which has been described in 6 previously reported cases with the same deletion involving 6q13q15. There was no recognizable abnormality of limbs or digits, and the autopsy did not identify defects involving the internal organs.     

A rare case of de novo distal 19q trisomy prenatally diagnosed

We present a case of de novo trisomy of distal 19q diagnosed prenatally by cytogenetics and FISH analysis. The autopsy performed after termination of the pregnancy showed major internal and external malformations that are associated with this chromosome abnormality.     

Interstitial deletion del(10)(q25.2q25.3 approximately 26.11)--case report and review of the literature

OBJECTIVES: To present the clinical, cytogenetic, and molecular cytogenetic findings of prenatally diagnosed interstitial deletion 10q25.2-q26.1. The majority of distal 10q deletions are pure terminal deletions with breakpoints in 10q25 and 10q26. Only four patients have been described so far with interstitial deletions involving bands 10q25.2-q26.1. METHODS: Postmortem physical examination and autopsy of the foetus after medically terminated pregnancy. GTG-banding, reverse painting, and FISH analysis with BAC clones on amniocyte metaphases were performed to determine the extent of the deletion. RESULTS: At 20 weeks the eutrophic female foetus showed pronounced microretrogeny and hypertelorism, clubfeet as well as minor internal anomalies like pancreas anulare, atypically lobed liver, and missing choleocystis. Cardiac anomalies were not observed and the genitalia were of a normal female. The deletion encompasses 6-Mb and is associated with hemizygosity for 30 genes, including the genes for beta-tectorin, the beta-1 adrenergic receptor, and the alpha-2A adrenergic receptor. CONCLUSION: An interstitial deletion del(10)(q25.2q25.3 approximately 26.11) was confirmed by FISH with mapped BAC clones. Clinical and molecular cytogenetic analyses of further interstitial 10q deletions are necessary to assess whether the phenotypic manifestations differ between deletions that are interstitial compared to those that include also the terminal region of chromosome 10.     

Prenatal diagnosis of mosaic distal 5p deletion and review of the literature

OBJECTIVES: To present the prenatal diagnosis of mosaic distal 5p deletion and a review of the literature. CLINICAL SUBJECT AND METHODS: A 37-year-old woman, gravida 2, para 1, underwent genetic amniocentesis at 17 weeks' gestation because of advanced maternal age. Cytogenetic analysis of the cultured amniocytes revealed mosaicism for a distal 5p deletion, mos 46,XX,del(5)(p15.1)/46,XX (23 colonies/23 colonies). Repeat amniocentesis showed a consistent karyotype of mos 46,XX,del(5)(p15.1)/46,XX (12 colonies/15 colonies). The parental karyotypes were normal. Prenatal ultrasound demonstrated microcephaly and cerebellar hypoplasia. The pregnancy was terminated at 21 weeks' gestation. Postnatally, the fetus displayed microcephaly, a triangular face, hypertelorism, epicanthic folds, down-slanting palpebral fissures, low-set ears, and micrognathia. A karyotype of mos 46,XX,del(5)(p15.1)/46,XX was found in the cord blood, liver, lungs, and skin, whereas the placenta had a different karyotype of mos 46,XX,dup(5)(qter-->p15.3::p15.3-->p10)/46,XX, and the karyotype of the amnion was mos 46,XX,del(5)(p15.1)/46,XX,dup(5)(qter-->p15.3::p15.3-->p10)/46,XX,trp(5)(qter-->p15.3::p15.3-->p10::p10-->p15.3)/46,XX. The deletion, duplication, and triplication of the terminal region of the short arm of chromosome 5 were confirmed by the studies of fluorescence in situ hybridization. CONCLUSION: The cri-du-chat syndrome can be identified prenatally because of advanced maternal age, familial cri-du-chat syndrome, parental balanced translocations involving chromosome 5, sonographically detected fetal structural abnormalities, and/or an abnormal maternal serum test. Fetuses with the mosaic distal 5p deletion may be associated with the sonographic findings of microcephaly and cerebellar hypoplasia, and fetoplacental and fetoamnionic chromosomal discrepancies.     

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.     

5p15缺失综合征合并4q32重复1例临床分析与基因诊断

目的 探讨5p15缺失综合征合并4q32重复的临床特征及分子遗传学特点.方法 回顾分析1例5p15缺失综合征合并4q32重复患儿的临床资料以及分子遗传学分析资料.结果 10月龄女性患儿,具有特殊面容、发育迟缓、先天性心脏病及喉软骨发育不良等临床表现.全外显子测序和染色体组拷贝数分析精确定位拷贝数异常改变的染色体片段区域...     

Large interstitial deletion of chromosome 13q and severe short stature: clinical report and review of the literature

We report a 16 year old African American female with an interstitial deletion of chromosome 13 comprising approximately 40% of the long arm of this chromosome [karyotype 46,XX, del(13)(q14.12q31.2)]. We believe that this case is interesting because of the large size of the chromosome deletion, the severe growth retardation seen in the proband and her prolonged survival.     

Molecular cytogenetic characterization of 2q deletion and Xq duplication associated with nasal bone dysplasia in prenatal diagnosis: A case report and literature review

ObjectiveWe report a prenatal case of male fetus with a 2q13 deletion and an Xq27.3q28 duplication, presenting nasal bone dysplasia by ultrasound examination. And we compare the similarities of clinical features of cases consisting of similar 2q deletion and Xq duplication.Case reportA 30-year-old woman was referred for prenatal diagnosis and genetic counseling at 24 weeks of gestation. Prenatal ultrasound showed nasal bone dysplasia of the fetus. Amniocentesis revealed the karyotype of the fetus as 46, XY and the results of chromosomal microarray analysis was arr[GRCh37] 2q13(110467258–111370025)x1, arr[GRCh37]Xq27.3q28(144050780–149748782)x2. The parents both have normal karyotypes. The couple chose to continue the pregnancy and finally delivered a male infant at 39 weeks of gestation. His weight was 2850 g and length was 50 cm. Physical examination of the newborn revealed no apparent anomalies. Until the boy was one year old, there was no abnormalities in his growth and development. The long-term follow-up till adulthood for the healthy infant is necessary.ConclusionThe development of CMA plays a critical role in prenatal diagnosis and genetic counseling for unidentified chromosomal anomalies. More clinical information and further studies of patients with these anomalies will identify the pathogenicity of the involving genes and improve the understanding of the phenotype–genotype correlation.     

Prenatal diagnosis of de novo interstitial 2q14.2-2q21.3 deletion assisted by array-based comparative genomic hybridization: a case report

BACKGROUND: During conventional karyotyping, it can be difficult to clearly identify de novo interstitial deletion of a chromosomal band when there are similar bands nearby. CASE: A 38-year-old, pregnant woman underwent genetic amniocentesis at 18 weeks of gestation due to advanced maternal age. Chromosomal studies detected an interstitial deletion at the long arm of 1 chromosome 2. Array-based comparative genomic hybridization further located the deletion in the band of interstitial 2q14.2-2q21.3. Prenatal ultrasound revealed borderline ventriculomegaly without additional abnormalities of the cardiovascular, urinary or gastrointestinal systems or the spine. Fetal magnetic resonance imaging identified mild dilatation of the posterior horns of the lateral ventricles. At 5 months after birth, the infant had febrile convulsions that were well controlled with medication. A single incisor was noted at 1 year of age. Atrophy of the left, undescended testis and developmental delay were also noted. CONCLUSION: Array-based comparative genomic hybridization is helpful in prenatal diagnosis because it can precisely locate the chromosome bands with copy number changes. Clinical manifestations in this case provide valuable information for genetic counseling pregnant women who conceive a fetus with deletion of interstitial 2q14.2-2q21.3.     

Molecular cytogenetic analysis and clinical findings in a newborn with prenatally diagnosed rec(7)dup(7q)inv(7)(p22q31.3)pat

We report prenatal and early postnatal findings in a newborn with a partial trisomy of chromosome 7 (7q31.3-qter), arising from meiotic recombination of a paternal pericentric inversion, inv(7)(p22q31.3). The inversion breakpoints were localized and the regions of duplication and deletion were defined by fluorescence in situ hybridization (FISH) analysis using a series of locus-specific and subtelomeric probes. To our knowledge, only three cases involving a recombinant 7 with duplication of 7q have been reported, two of these being first cousins. The clinical findings in our patient included skeletal abnormalities, facial dysmorphism, dilated cerebral ventricles, microretrognathia and short neck. These findings and some aspects of the neonatal course were consistent with the phenotype previously reported for duplication of distal 7q, without associated monosomy for sequences from another chromosome.     

Molecular genetic characterization of a prenatally detected de novo interstitial deletion of chromosome 20p (20p12-p13) encompassing JAG1 and a literature review of prenatal diagnosis of Alagille syndrome

Objective

We present prenatal diagnosis and molecular genetic characterization of a de novo interstitial deletion of chromosome 20p (20p12-p13) and a literature review of prenatal diagnosis of Alagille syndrome (ALGS).

Molecular screening of the ZFHX1B gene in prenatally diagnosed isolated agenesis of the corpus callosum

OBJECTIVE: Agenesis of the corpus callosum (ACC) is the most common malformation of the central nervous system and may be associated with mental retardation. ACC is found in 40% of the cases of Mowat-Wilson syndrome (MWS), a polytopic embryonic defect including a distinctive facial gestalt, severe mental retardation, epilepsy and postnatal microcephaly as constant features. Other manifestations involve Hirschsprung disease, cardiac defects, renal abnormalities and hypospadias. Among this broad spectrum of malformations recently associated with haploinsufficiency of the zinc finger homeobox 1B gene (ZFHX1B), ACC can therefore be the only feature to be detected prenatally. Thus, we studied a group of 18 fetuses terminated for ACC and performed mutational analysis of the ZFHX1B gene in six selected cases. METHODS: Diagnosis of agenesis of the ACC was performed by prenatal echography survey. Screening for ZFHX1B deletions was performed by poly (CA) microsatellite markers studies and real-time semi-quantitative PCR. Mutational analysis was performed by single-strand conformation polymorphisms analysis (SSCP). RESULTS: Neither deletion encompassing the ZFHX1B locus nor mutation could be detected in any of the six fetuses analysed. CONCLUSION: ZFHX1B is not a major gene in isolated ACC. However, analysis of MWS should be considered in the differential diagnosis of ACC, especially when the facial features raise the possibility of MWS.