Deletion (9) (p13.1 p21.1)

We report on a 22‐month‐old girl with minor facial anomalies, global developmental delay, growth retardation, seizures, and leukoencephalopathy. Initial clinical assessment suggested the diagnosis of Williams syndrome. Results of fluorescence in situ hybridization testing for elastin were normal. However, chromosome analysis showed a 46,XX,del(9)(p13.1p21.1) karyotype in peripheral lymphocytes. Parental chromosomes were normal, indicating a de novo deletion. This patient's manifestations are compared with those of two other cases with overlapping deletions of the proximal short arm of chromosome 9. Am. J. Med. Genet. 91:113–115, 2000. © 2000 Wiley‐Liss, Inc.     

Deletion (9) (p13.1 p21.1)

We report on a 22-month-old girl with minor facial anomalies, global developmental delay, growth retardation, seizures, and leukoencephalopathy. Initial clinical assessment suggested the diagnosis of Williams syndrome. Results of fluorescence in situ hybridization testing for elastin were normal. However, chromosome analysis showed a 46,XX,del(9)(p13.1p21.1) karyotype in peripheral lymphocytes. Parental chromosomes were normal, indicating a de novo deletion. This patient's manifestations are compared with those of two other cases with overlapping deletions of the proximal short arm of chromosome 9.     

Del(3) (p25.3) without phenotypic effect.

A terminal deletion of chromosome 3 at p25.3 was observed during prenatal diagnosis. A similar deletion is also present in the phenotypically normal mother. The deletion was confirmed by FISH. The breakpoint is distal to the region responsible for the 3p- syndrome. A normal baby girl was born with no apparent phenotypic abnormalities.     

Isochromosome (6p) in Waldenstrom's macroglobulinemia.

Cytogenetic data on two cases of previously treated Waldenstrom's macroglobulinemia (WM) are presented. An i(6p) was identified in 60 and 56% of bone marrow (BM) metaphases from each patient, respectively. In both cases, i(6p) occurred as part of a complex karyotype but was also observed as the sole abnormality in a proportion of metaphases. The literature on the cytogenetics of WM and the relevance of i(6p) is discussed.     

De novo deletion (2) (p11.2p13): clinical, cytogenetic, and immunological data.

We report a case of a boy with a de novo interstitial deletion of chromosome (2) (p11.2p13). Clinical features included dysmorphism of the face, genital region, and limbs, psychomotor retardation, and vitiligo. A reduced ratio of immunoglobulin (Ig) light chain expression (kappa/lambda ratio: 0.7) was found, compatible with deletion of one Ig kappa allele on chromosome 2p12. The patient had no clinical or laboratory signs of immunodeficiency.     

Implantation of p(HEMA)-collagen composite into bone.

The replacement of bone defects is very important in clinical practice. This study compares biological properties of poly(2-hydroxyethyl methacrylate)-collagen composite with those exhibited by pure p(HEMA), an insoluble fraction of calf skin collagen (ISC-40) and demineralized bone matrix after implantation into pig or dog femurs. The levels of biodegradation or destruction of implants and healing of bone defects were studied using X-ray photography, histology and enzyme histochemistry. The results indicated a significant effect of collagen on biological destruction of the p(HEMA)-composite implants; even a minute amount of collagen influences this process dramatically. A stimulatory action of collagen on new bone formation may be of importance in bone defect healing.     

Duplication (17p) in a child with an isodicentric (17p) chromosome

We present a child with multiple structural defects due to duplication of the short arm and a small portion of the long arm of chromosome 17. Three children with similar cytogenetic abnormalities have been reported previously. The karyotype contained an isodicentric chromosome derived from chromosome 17. A clue to the mechanism that produced the isochromosome was retained in the genome in the form of a part of the chromosome 17 long arm which was attached to the short arm of a chromosome 10.     

Trisomy 17p due to a t(8; 17) (p23; p11.2)pat translocation. Case report and review of the literature

We describe a female newborn girl with partial trisomy 17p, which was not detected at the initial cytogenetic investigation, but which later proved to be an unbalanced product of a paternal translocation t(8; 17)(p23;pl 1.2). Comparison with the three previously reported patients suggests a clinically distinct "trisomy 17p syndrome", i.e. pre- and postnatal growth retardation, microcephaly, antimongoloid slanting of palpebral fissures, hypertelorism, long philtrum with thin upper lip, micrognathia and high-arched palate. Two of the four patients had a heart defect, and psychomotor developmental delay was evident in all four cases. In the present patient, the chromosomal anomaly was only detected after the finding of the autosomal reciprocal translocation in the father. The importance of cytogenetic investigations in parents of a MCA/MR child with apparently normal chromosomes is emphasized.     

FISH analysis in detecting 9p duplication (p22p24)

Authors report on a case of partial 9p duplication, involving the 9p22-9p24 region. This represents the second case of such duplication in which the breakpoints were precisely defined using fluorescence in situ hybridisation (FISH) with chromosome 9 specific painting and YAC DNA probes, localised onto 9p22-9p24 region. FISH analysis pinpointed chromosome breakpoints in dup(9)(p22p24) and excluded an insertion or a translocation from other chromosomes. The present report supports the segment 9p22-9p24 as the critical region for the observed phenotype of the duplication 9p syndrome.     

Rare interstitial deletion (2)(p11.2p13) in a child with pericentric inversion (2)(p11.2q13) of paternal origin.

An unbalanced 46,XY,der(2)del(2)(p11.2p13) inv(2)(p11.2q13) karyotype was found in a phenotypically abnormal child with a de novo interstitial deletion of band 2p12 associated with an inv(2)(p11.2q13) inherited from the father. The inv(2) is generally considered a benign familial variant without significant reproductive consequences. However, our findings led us to consider a previously proposed mechanism of unequal meiotic crossing over at the base of a parental inversion loop, which could lead to either a deletion or duplication of a segment adjacent to the inverted region in the offspring. This phenomenon has been reported in other inversions of chromosomes 1, 7, 13, 15, and 17 and may explain the origin of the deletion in our patient. Although repetitive sequences might be present around such inversions, which could predispose to de novo deletions independently of the inversion, current evidence including this case favors a proposed causal relationship between the parental inversion and the deletion in the child. Our review and results suggest there could be a small risk for a related imbalance to couples with an inv(2)(p11.2q13). For del(2)(p11.2p13), which is rare, a more distinct phenotype has been proposed herein. Our patient shared several findings with the three previously published cases, namely the broad nasal bridge, abnormal ears, high-arched palate, psychomotor retardation, and micrognathia. However, our patient also had sensorineural hearing loss and significant hypotonia, which have not been previously reported, thereby expanding our understanding of this rare deletion. Am. J. Med. Genet. 87:139-142, 1999. Published 1999 Wiley-Liss, Inc.     

Allelic discrimination of cis-trans relationships by digital polymerase chain reaction: GJB2 (p.V27I/p.E114G) and CFTR (p.R117H/5T)

PurposeTo distinguish the cis-trans relationship of two sequence changes and to arrive at an accurate molecular diagnosis for autosomal recessive disorders, methods such as Sanger sequencing cannot differentiate whether sequence changes are in cis or trans. In addition, most techniques theoretically appropriate for allelic discrimination depend on the specific identified sequence changes for assay design, need extensive optimization, or may not be suitable. We developed a method that does not fully depend on the specific nucleotide changes. It enables efficient assay design and practical implementation of allelic discrimination.MethodsDigital polymerase chain reaction (PCR) was used to separate and amplify alleles. Sanger sequencing was subsequently used to identify sequence changes.ResultsWe developed a cost-effective digital PCR method for allelic discrimination of short amplicons and demonstrated it with p.Val27Ile and p.Glu114Gly in GJB2 as an example. We also successfully developed a long-range digital PCR approach to determine the cis-trans relationship of p.Arg117His and 5T in the CFTR gene.ConclusionDigital PCR for allelic discrimination can be clinically implemented to determine the allelic configuration of relatively common sequence changes which frequently appear together and have clinical ramifications, such as the combination of p.Val27Ile and p.Glu114Gly in the GJB2 gene and p.Arg117His and 5T in CFTR.     

Familial del(18p) syndrome

We report on sibs and their mother, all with del(18p). The propositus, an 11‐month‐old, had developmental delay, round face, hypertelorism, large ears, broad nasal bridge, upturned nostrils, micrognathia, a high palate, redundant skin around the neck, micropenis, and cryptorchidism . The elder sister, a two and 7/12‐year‐old, had round face, hypertelorism, broad nasal bridge, narrow and high palate, redundant skin around the neck, short fingers, and hypoplastic genitalia. Their mother had microcephaly, hypertelorism, prominent colu‐ mella, broad nasal bridge, wide mouth, high palate, malaligned teeth, and clinodactyly of the fifth fingers. Serial photographs of the mother showed that the characteristic round face in infancy changed to long face with age. The present report suggests that the mother with del(18p) may be fertile, and proper genetic counseling and long follow‐up is necessary for the patient with del(18p) syndrome. © Wiley‐Liss. Inc.     

Interstitial deletion of chromosome 2 (p23p25)

We report a patient with a de novo interstitial deletion of the short arm of chromosome 2 (p23p25). The patient had microcephaly with prominent forehead and occiput, narrow rectangular face, clinodactyly, failure to thrive, delayed psychomotor development, and seizures. Maternal serum alpha-fetoprotein was undetectable at 18 weeks of gestation. Heterozygosity at the red cell acid phosphatase locus (SRO-2p25) and normal levels of red cell malate dehydrogenase (SRO-2p23) are findings consistent with the presence of genetic material from bands 2p25 and 2p23.     

The dup(17p) syndrome

In a 42-month-old girl a duplicated 17p chromosome anomaly was identified by trypsin-Giemsa banding techniques. The clinical findings are compared with those of previous case reports. Common phenotypics changes include failure to thrive; hypoplastic, apparently low-set ears; micrognathia; flexion abnormalities of fingers; and foot abnormalities.     

Molecular cytogenetic characterization of a familial der(1)del(1)(p36.33)dup(1)(p36.33p36.22) with variable phenotype

Chromosome deletions involving 1p36 are the most common known terminal rearrangements occurring at a frequency of approximately 1 in 5,000 live births. In contrast, duplications of the same region have been reported rarely. We describe a familial rearrangement der(1)del(1)(p36.33)dup(1)(p36.33p36.22) identified in a mother, daughter, and son. These individuals help define a syndrome with variable mental disability, attention deficit-hyperactivity disorder, and a distinctive facial appearance with wide palpebral fissures, broad nasal root, macrostomia, ear malformations, and prominent incisors. Based on our results we suggest that the complex rearrangement seen in our family could be the result of the breakage-fusion-bridge (BFB) cycles model of formation.     

Familial Del(18p) syndrome

We report on sibs and their mother, all with del(18p). The propositus, an 11-month-old, had developmental delay, round face, hypertelorism, large ears, broad nasal bridge, upturned nostrils, micrognathia, a high palate, redundant skin around the neck, micropenis, and cryptorchidism. The elder sister, a two and 7/12-year-old, had round face, hypertelorism, broad nasal bridge, narrow and high palate, redundant skin around the neck, short fingers, and hypoplastic genitalia. Their mother had microcephaly, hypertelorism, prominent columella, broad nasal bridge, wide mouth, high palate, malaligned teeth, and clinodactyly of the fifth fingers. Serial photographs of the mother showed that the characteristic round face in infancy changed to long face with age. The present report suggests that the mother with del(18p) may be fertile, and proper genetic counseling and long follow-up is necessary for the patient with del(18p) syndrome. Copyright Wiley-Liss. Inc.     

Nonrandom association of atrioventricular canal and del (8p) syndrome.

We describe a patient with partial deletion of the short arm of chromosome 8 with an atrioventricular canal. This type of congenital heart defect was found in 4 of the 7 previously reported del (8p) children with a congenital heart defect in which the cardiac assessment was complete. The prevalence of an atrioventricular canal in this aneuploidy is high and suggests a nonrandom association of the 2 anomalies.