Proximal Interstitial Deletion Research Articles

Clinical and molecular cytogenetic studies of five new patients with 20q11q12 deletion and review of the literature: Proposition of two critical regions.

Deletions of the long arm of chromosome 20 (20q) are rare, with only 16 reported patients displaying a proximal interstitial 20q deletion. A 1.62 Mb minimal critical region at 20q11.2, encompassing three genes GDF5, EPB41L1, and SAMHD1, is proposed to be responsible for this syndrome. The leading clinical features include growth retardation, intractable feeding difficulties with gastroesophageal reflux, hypotonia and psychomotor developmental delay. Common facial dysmorphisms including triangular face, hypertelorism, and hypoplastic alae nasi were additionally reported. Here, we present the clinical and molecular findings of five new patients with proximal interstitial 20q deletions. We analyzed the phenotype and molecular data of all previously reported patients with 20q11.2q12 microdeletions, along with our five new cases. Copy number variation analysis of patients in our cohort has enabled us to identify the second critical region in the 20q11.2q12 region and redefine the first region that is initially identified. The first critical region spans 359 kb at 20q11.2, containing six MIM genes, including two disease-causing genes, GDF5 and CEP250. The second critical region spans 706 kb at 20q12, encompassing four MIM genes, including two disease-causing genes, MAFB and TOP1. We propose GDF5 to be the primary candidate gene generating the phenotype of patients with 20q11.2 deletions. Moreover, we hypothesize TOP1 as a potential candidate gene for the second critical region at 20q12. Of note, we cannot exclude the possibility of a synergistic role of other genes involved in the deletion, including a contiguous gene deletion syndrome or position effect affecting both critical regions. Further studies focusing on patients with proximal 20q deletions are required to support our hypothesis.

Familial 4p Interstitial Deletion Provides New Insights and Candidate Genes Underlying This Rare Condition

Chromosome 4p deletions can lead to two distinct phenotypic outcomes: Wolf--Hirschhorn syndrome (a terminal deletion at 4p16.3) and less frequently reported proximal interstitial deletions (4p11-p16). Proximal 4p interstitial deletions can result in mild to moderate intellectual disability, facial dysmorphisms, and a tall thin body habitus. To date, only 35 cases of proximal 4p interstitial deletions have been reported, and only two of these cases have been familial. The critical region for this syndrome has been narrowed down to 4p15.33-15.2, but the underlying causative genes remain unclear. In this study, we report the case of a 3-year-old female with failure to thrive, developmental and motor delays, and morphological features. The mother also had a 4p15.2-p14 deletion, and the proband was found to have a 13.4-Mb 4p15.2-p14 deletion by chromosome microarray analysis. The deleted region encompasses 16 genes, five of which have a high likelihood of contributing to the phenotype: PPARGC1A, DHX15, RBPJ, STIM2, and PCDH7. These findings suggest that multiple genes are involved in this rare proximal 4p interstitial deletion syndrome. This case highlights the need for healthcare providers to be aware of proximal 4p interstitial deletions and the potential phenotypic manifestations.

Prenatal diagnosis and molecular cytogenetic characterization of an interstitial deletion of 18q12.1-q12.3 encompassing DTNA, CELF4 and SETBP1

ObjectiveWe present prenatal diagnosis and molecular cytogenetic characterization of an interstitial deletion of 18q12.1-q12.3. Case reportA 35-year-old woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XX,del(18)(q12.1q12.3). The fetal ultrasound was unremarkable. The woman underwent repeat amniocentesis at 20 weeks of gestation. Array comparative genomic hybridization (aCGH) using uncultured amniocytes revealed a 10.76-Mb interstitial deletion 18q12.1-q12.3 or arr 18q12.1q12.3 (31,944,347–42,704,784) × 1.0 encompassing 19 Online Mendelian Inheritance of in Man (OMIM) genes including DTNA, CELF4 and SETBP1. Metaphase fluorescence in situ hybridization analysis on cultured amniocytes confirmed an 18q proximal interstitial deletion. The parental karyotypes were normal. Polymorphic DNA marker analysis determined a paternal origin of the deletion. The pregnancy was subsequently terminated at 24 weeks of gestation, and a 650-g fetus was delivered with characteristic facial dysmorphism. ConclusionaCGH analysis and polymorphic DNA marker analysis at amniocentesis are useful for determination of the deleted genes and the parental origin of the de novo deletion, and the acquired information is helpful for genetic counseling.

3p14 De Novo Interstitial Microdeletion in a Patient with Intellectual Disability and Autistic Features with Language Impairment: A Comparison with Similar Cases.

To date, few cases of 3p proximal interstitial deletions have been reported and the phenotype and genotype correlation is not well understood. Here, we report a new case of a 3p proximal interstitial deletion. The patient is an 11-year-old female with speech and social interaction difficulties, learning disability, and slight facial dysmorphism, but no other major malformations. An 8 Mb de novo interstitial deletion at 3p14.2-p14.1, from position 60.461.316 to 68.515.453, was revealed by means of array comparative genomic hybridization and confirmed using quantitative reverse-transcription polymerase chain reaction assays. This region includes six genes: FEZF2, CADPS, SYNPR, ATXN7, PRICKLE, and MAGI1, that are known to have a role in neurodevelopment. These genes are located on the proximal side of the deletion. We compare our case with previously well-defined patients reported in the literature and databases.

1p36 Deletions in Two Cases with Thalassemia

ABSTRACTSummaryTerminal deletions in the short arm of chromosome one are generally associated with characteristic phenotype with dysmorphic features, including congenital anomalies and mental retardation with various degrees. Different outcomes depend on the sizes and locations of the deleted areas characterized by moderate to severe intellectual disability, delayed growth, hypotonia, seizures, limited speech ability, malformations, hearing and vision impairment and distinct facial features. The symptoms may vary, depending on the exact location of the chromosomal deletion but not a single reported case showed any ‘feature of anemia’.We report here one male and one female individual with partial deletions on chromosome no. one, both at 1p36 region. Cytogenetic analysis of blood lymphocytes was studied with high resolution GTG-banding analysis, using cyto-vision software on their chromosomes. Results revealed 46, XY, del(1)(p36.21) in the male who was also diagnosed as a ‘beta thalassemia trait’ and the other case was 46, XX, del(1)(p36.3) in the female who was diagnosed as a case of ‘HbE-beta thalassemia’.This report provides additional cases to the growing literature.Purpose/backgroundDeletion 1p36 is the most common terminal deletion syndrome with an estimated occurrence of 1:5000 live births. We report two patients with 1p36 deletions among which one shows ‘atypical’ proximal interstitial deletion at 1p36.21 using HR-GTG banding analysis. Interestingly, both the patients manifest one extra clinical characteristic that is different from those seen in ‘classical’ monosomy 1p36 syndrome, is ‘microcytic anemia’.Based on the analysis of the clinical and molecular data from our patients and those reported in the literature, we suggest that deletion 1p36.21 chromosomal abnormality may constitute yet another deletion syndrome distinct from the classical distal 1p36 deletion syndrome.Our aim was to find out further information regarding anemia since there are previously reported cases of anemias associated with this 1p36 region—one is presence of a ‘putative tumor suppressor gene’ important in the evolution of chronic myelocytic leukemia and the other is one inherited erythroblastopenia, commonly known as ‘Diamond-Blackfan anemia’ (DBA), caused by mutation in the gene encoding ribosomal protein L11 (RPL11) to answer families’ questions in the clinical setting.Materials and methodsStandard cytogenetic analysis was used with high resolution GTG-banding analysis, using cytovision software for karyotyping and high performance liquid chromatography (HPLC) and amplification refractory mutation mutation system (ARMS-PCR) to detect the five common Indian b-thalassemia mutations: [IVS-I-5 (G >C), Cod 15 (G-A), Cod 8/9 (+G), Fr 41/42 (–TTCT) and Cod 26 (G-A)].ResultsResults showed 46, XY, del(1)(p36.21) in the male, additionally diagnosed as a ‘beta thalassemia trait’ and in another case 46, XX, del(1)(p36.3) in female who was diagnosed as a case of ‘HbE-beta thalassemia’.ConclusionThese two patients with deletion 1p36 represent association with other genetic disorder which is characterized by hematological abnormalities.How to cite this articleDe P, Chakravarty S, Chakravarty A. 1p36 Deletions in Two Cases with Thalassemia. Int J Infertil Fetal Med 2014;5(2):69-74.

Endocrine phenotype of 6q16.1–q21 deletion involving SIM1 and Prader–Willi syndrome‐like features

Proximal interstitial 6q deletion involving Single-minded 1 (SIM1) gene causes a syndromic form of obesity mimicking Prader-Willi syndrome. In addition to obesity, Prader-Willi syndrome includes several other endocrinopathies, such as hypothyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. The endocrine phenotype of interstitial 6q deletion remains largely unknown, although clinical similarities between Prader-Willi syndrome and interstitial 6q deletion suggest endocrine abnormalities also may contribute to the interstitial 6q deletion phenotype. This report describes the endocrine phenotype in a propositus with the Prader-Willi-like syndrome associated with an interstitial 6q deletion including the SIM1 gene. Detailed endocrine evaluation of the propositus during childhood and adolescence revealed hypopituitarism, though initial endocrine evaluations during infancy were unremarkable. Our patient raises the possibility that hypopituitarism may be part of the phenotype, especially short stature, caused by interstitial 6q deletion. SIM1 plays an important role in the development of neuroendocrine lineage cells, implicating SIM1 haploinsufficiency in the pathophysiology of hypopituitarism seen in our propositus. Early identification of endocrine abnormalities can improve clinical outcome by allowing timely introduction of hormone replacement therapy. Hence, we suggest that detailed endocrine evaluation and longitudinal endocrine follow up be performed in individuals with proximal interstitial 6q deletion involving SIM1.

Prenatal diagnosis and molecular cytogenetic characterization of a de novo proximal interstitial deletion of chromosome 4p (4p15.2→p14)

We present prenatal diagnosis of de novo proximal interstitial deletion of chromosome 4p (4p15.2→p14) and molecular cytogenetic characterization of the deletion using uncultured amniocytes. We review the phenotypic abnormalities of previously reported patients with similar proximal interstitial 4p deletions, and we discuss the functions of the genes of RBPJ, CCKAR, STIM2, PCDH7 and ARAP2 that are deleted within this region.

First report of a de novo 18q11.2 microdeletion including GATA6 associated with complex congenital heart disease and renal abnormalities

Deletions of the long arm of chromosome 18 have been previously reported in many patients. Most cases involve the more distal regions of the long arm (18q21.1->qter). However, proximal interstitial deletions involving 18q11.2 are extremely rare. Here we report on a 14-month-old female with a 4.7 Mb (19,667,062-24,401,876 hg19) de novo interstitial deletion within chromosomal band 18q11.2, which includes GATA6 and 24 other RefSeq genes. The clinical features of our patient include complex congenital heart defects, a double outlet right ventricle, a subaortic ventricular septal defect, D-malposed great arteries, an atrial septal defect, a dysplastic aortic valve and patent ductus arteriosus. In addition, she had renal anomalies-a duplicated collecting system on the left and mild right hydronephrosis. These heart and renal defects are not reported in other patients with 18q proximal interstitial deletions. Heterozygous point mutations in GATA6, encoding for a zinc finger transcription factor, have been shown to cause congenital heart defects. Given the well-established biological role of GATA6 in cardiac development, a deletion of GATA6 is very likely responsible for our patient's complex congenital heart defects. This is the smallest and most proximal 18q11.2 deletion involving GATA6 that is associated with complex congenital heart disease and renal anomalies.

Novel Proximal 14q Deletion: Clinical and Diffusion Tensor Imaging Tractography Findings in a Patient with Lissencephaly, Agenesis of the Corpus Callosum, and Septo-Optic Dysplasia

We report the unique CNS findings in a patient with a proximal chromosome 14q interstitial deletion. Conventional MR imaging allowed the clear delineation of agenesis of the corpus callosum, SOD, and diffuse lissencephaly. DTI tractography played a significant role in the evaluation of the proximal 14q deletion-associated abnormalities, delineating the extent of the dysmorphic connections of the Probst bundles and clarifying that apparent areas of heterotopias were the corticospinal tracts.

A de novo deletion of 20q11.2–q12 in a boy presenting with abnormal hands and feet, retinal dysplasia, and intractable feeding difficulty

Proximal interstitial deletions involving 20q11-q12 are very rare. Only two cases have been reported. We describe another patient with 20q11.21-q12 deletion. We precisely mapped the 6.5-Mb deletion and successfully determined the deletion landmarks at the nucleotide level. Common clinical features among the three cases include developmental delay, intractable feeding difficulties with gastroesophageal reflux, and facial dysmorphism including triangular face, hypertelorism, and hypoplastic alae nasi, indicating that the 20q11.2-q12 deletion can be a clinically recognizable syndrome. This is also supported by the fact that the three deletions overlap significantly. In addition, unique features such as arthrogryposis/fetal akinesia (hypokinesia) deformation and retinal dysplasia are recognized in the patient reported herein.

Clinical and molecular characterization of two patients with a 6.75 Mb overlapping deletion in 8p12p21 with two candidate loci for congenital heart defects

Clinical and molecular characteristics of two patients with a 6.75 Mb overlapping interstitial deletion in the 8p12p21 region are described and compared with previously reported cases with an overlapping deletion. The most common characteristics of interstitial deletions of proximal 8p are developmental delay, postnatal microcephaly and growth retardation. Other frequently reported findings are hypogonadism associated with haploinsufficiency of GNRH1 and ocular problems. Congenital heart anomalies are also common and might at least to some extent be due to haploinsufficiency of NKX2-6 or NRG1. The aforementioned clinical characteristics should be considered in the care of patients with a proximal interstitial 8p12p21 deletion.

Proximal interstitial 1p36 deletion syndrome: The most proximal 3.5-Mb microdeletion identified on a dysmorphic and mentally retarded patient with inv(3)(p14.1q26.2)

From the investigation by microarray-based comparative genomic hybridization (aCGH), a new syndrome with “atypical” proximal interstitial deletion of 1p36.23-36.11 has been suggested. Here, we report on an 8.5-year-old girl with psychomotor developmental delay and a dysmorphic appearance. Although her G-banded chromosomal analysis showed inv(3)(p14.1q26.2), detailed FISH analyses denied pathogenic deletions around the breakpoints of chromosome 3. Accordingly, aCGH analysis was performed to identify a genomic aberration related to her phenotype, and a 3.5-Mb interstitial deletion of 1p36.13-36.12 was revealed. This deletion was the most proximal interstitial deletion of 1p36. Compared to the previously reported patients, abnormally shaped teeth, delayed tooth eruption, and leg malformation are unique phenotypes only to this patient, which might be due to the centromeric unique deletion region with 0.8-Mb.

Periventricular heterotopia in a boy with interstitial deletion of chromosome 4p

We report on a 4-year-old boy with a proximal interstitial deletion in the short arm of chromosome 4p with the karyotype 46,XY,del(4)(p14p15.32),inv(9)(p13q13). For a precise delineation of the deleted region, an array-based comparative genomic hybridization (a-CGH) analysis was performed. The proband's phenotype and cytogenetic findings are compared with previously reported cases with proximal 4p deletion syndrome. The syndrome is associated with normal growth, varying degrees of mental retardation, characteristic facial appearance and minor dysmorphic features. Additionally, our patient developed a seizure disorder due to abnormal neuronal migration, i.e., periventricular heterotopia.

Identification of proximal 1p36 deletions using array‐CGH: a possible new syndrome

Monosomy 1p36 is the most common terminal deletion syndrome with an estimated occurrence of 1:5000 live births. Typically, the deletions span <10 Mb of 1pter-1p36.23 and result in mental retardation, developmental delay, sensorineural hearing loss, seizures, cardiomyopathy and cardiovascular malformations, and distinct facies including large anterior fontanel, deep-set eyes, straight eyebrows, flat nasal bridge, asymmetric ears, and pointed chin. We report five patients with 'atypical' proximal interstitial deletions from 1p36.23-1p36.11 using array-comparative genomic hybridization. Four patients carry large overlapping deletions of approximately 9.38-14.69 Mb in size, and one patient carries a small 2.97 Mb deletion. Interestingly, these patients manifest many clinical characteristics that are different from those seen in 'classical' monosomy 1p36 syndrome. The clinical presentation in our patients included: pre- and post-natal growth deficiency (mostly post-natal), feeding difficulties, seizures, developmental delay, cardiovascular malformations, microcephaly, limb anomalies, and dysmorphic features including frontal and parietal bossing, abnormally shaped and posteriorly rotated ears, hypertelorism, arched eyebrows, and prominent and broad nose. Most children also displayed hirsutism. Based on the analysis of the clinical and molecular data from our patients and those reported in the literature, we suggest that this chromosomal abnormality may constitute yet another deletion syndrome distinct from the classical distal 1p36 deletion syndrome.

A Case of Partial 14q- with Facial Features of Holoprosencephaly and Hydranencephaly

We report a rare case of facial features of holoprosencephaly associated with hydranencephaly, with a de novo proximal interstitial deletion of the long arm of chromosome 14, specifically, del(14)(q13q21). She was born at 37 weeks of gestation and transferred to our institution at 3 years of age. The patient had midline facial anomalies consisting of cleft palate, defective nasal septum, and hypotelorism, together with endocrine abnormalities such as diabetes insipidus and hypothyroidism. Cranial computed tomography revealed the near-total loss of all cerebral tissue, with a frontal part of the cerebral falx lacking. None of the few reports of holoprosencephaly with 14q- chromosomal abnormality describe holoprosencephaly in association with hydranencephaly. The partial deletion of chromosome 14, del(14)(q13q21), may underlie the association of facial features of holoprosencephaly and hydranencephaly.

Pediatric T-Cell Lymphoblastic Leukemia and T-Cell Lymphoblastic Lymphoma: Differences in the Common Deleted Region and the Prognostic Impact of Chromosome 6q Deletions.

Background/Objectives: Deletions of chromosome 6q have been reported in a variety of hematological malignancies. Regarding their prognostic impact, however, the data are inconclusive, as most of the published studies included different subtypes, different immunophenotypes and/or differently treated patients (pts).Therefore our analyses focused on 109 pediatric pts with T-cell lymphoblastic-lymphoma (T-LBL) compared with 127 pediatric pts with T-cell lymphoblastic leukemia (T-ALL). Both groups were treated uniformly according to the BFM-ALL-type treatment strategy.Design/Methods: Deletions of chromosome 6q were examined by loss-of-heterozygosity (LOH) analysis of 25 microsatellite-markers located on chromosome 6q14-q24. DNA samples were amplified by PCR, followed by fragment-length analysis on a genetic analyzer.Results: Between 03/95-06/04 a total of 217 pediatric T-LBL pts were registered at the NHL-BFM study center and treated uniformly with ALL-type treatment strategy. 109 T-LBL pts were evaluable for LOH analysis, including 21 out of 27 pts who suffered relapse. In the 109 pts a total of 1,688 markers were analyzed successfully. Patterns of LOH were detectable in 22 pts. Analysis of the putative deleted regions revealed LOH of all informative markers in 5 pts and interstitial deletions in 17 cases. A common deleted region of 13 cases was flanked by markers D6S1682 and D6S1716 at band 6q16. There were no statistically significant differences in LOH-positive versus LOH-negative T-LBL pts with respect to age, sex ratio, stage, BM or CNS involvement. However, detection of LOH at 6q14-24 was associated with poor outcome: Probability of disease-free-survival (DFS) was 91±3% for LOH-negative versus 38±11% for LOH-positive pts (p<0.0001).In comparison, a total of 186 T-ALL pts were consecutively registered in the trial ALL-BFM 2000 between 08/99-06/02. Of these, 127 pts were evaluable for LOH analysis, including 22 out of 27 pts with relapse. In the 127 pts a total of 3,109 markers were analyzed successfully. Patterns of LOH were detected in 16 pts with proximal interstitial deletions in 15 out of the 16 cases. The 4.3 Mb common deleted region was flanked by markers D6S1627 and D6S1644. There were no significant differences between LOH-positive versus LOH-negative pts neither in clinical characteristics nor in treatment response or outcome.Conclusions: The pattern of 6q-deletions as well as the prognostic impact differ between pediatric T-LBL and T-ALL. LOH at 6q is detectable in 20% of pediatric T-LBL compared with 13% of pediatric T-ALL. In T-ALL the common deleted region is localized in chromosomal band 6q14. LOH is not associated with clinical parameters or outcome. In T-LBL the most frequently deleted marker is localized in band 6q16 and detectable LOH is associated with poor outcome. A prospective analysis of a larger series of pts is necessary to confirm the prognostic value of 6q deletions in T-LBL.

Major feeding difficulties in the first reported case of interstitial 20q11.22‐q12 microdeletion and molecular cytogenetic characterization

We report on a 4-year-old female presenting with intrauterine growth retardation, facial dysmorphic features, major feeding difficulties with severe diarrhea and vomiting, mental retardation with abnormal behavior and hypertonia. Feeding difficulties were the most invalidating features with absent oral intake requiring persistent enteral feeding. Standard cytogenetic studies were normal, but high-resolution chromosome analyses revealed a small de novo interstitial deletion of the long arm of chromosome 20, 46,XX,del(20)(q11.21q12). The deletion was confirmed using metaphase comparative genomic hybridization (CGH) and multicolor high resolution banding (mBAND). The deletion breakpoints were characterized using FISH analyses with YACs, PACs, and BACs clones located in the deleted and adjacent regions. A 6.6-Mb deleted region between markers D20S815 (20q11.22) and D20S435 (20q12) could be delineated. None of the nine previously reported cases with interstitial 20q deletion found in the literature involve the same breakpoints. This report further emphasizes the indication of high-resolution chromosome analyses in children with syndromic mental retardation. The description of additional cases would be useful in order to better characterize the phenotype of patients with proximal interstitial 20q deletion.

Rare proximal interstitial deletion of chromosome 4q, del(4)(q13.2q21.22): New case and comparison with the literature

Rare proximal interstitial deletion of chromosome 4q, del(4)(q13.2q21.22): New case and comparison with the literature

Prenatal diagnosis ofde novo proximal interstitial deletion of 9q and review of the literature of uncommon aneuploidies associated with increased nuchal translucency

To present the prenatal diagnosis and molecular cytogenetic analysis of de novo proximal interstitial deletion of 9q and to review the literature of uncommon aneuploidies associated with increased nuchal translucency (NT). Obstetric ultrasound at 11 weeks' gestation revealed an increased NT thickness of 6.6 mm in a 31-year-old primigravid woman. At 13 weeks' gestation, repeat ultrasound examinations revealed a normal NT thickness of 1.8 mm. The subcutaneous nuchal fluid accumulation was no longer present at the following ultrasound scans. An amniocentesis was performed at 18 weeks' gestation. Cytogenetic analysis revealed a karyotype of 46,XX,del(9)(q21.1q22.2). The parental karyotypes were normal. At 21 weeks' gestation, a 442-g female fetus was delivered with low-set ears, hypertelorism, and a thick nuchal fold. The parental origin of the interstitial deletion of 9q was analyzed with polymorphic DNA markers. With the microsatellite markers D9S238 (9q13), D9S889 (9q21.11), and D9S253 (9q22.2), two alleles inherited from the parents were seen in the proband, but with markers D9S1780 (9q21.31), D9S303 (9q21.32), D9S252 (9q21.33), and D9S316 (9q22.1), only one maternal allele was present. The deletion was of paternal origin. Fetuses with uncommon aneuploidies may manifest increased NT in the first trimester. The present case provides evidence for a correlation between increased NT and interstitial 9q deletion. Prenatal identification of increased NT should alert subtle structural chromosome aberrations and prompt high-resolution karyotyping.

Molecular mapping of deletion breakpoints on chromosome 4 of Drosophila melanogaster.

As part of our effort to induce and identify mutations in all genes on chromosome 4 of Drosophila melanogaster, we have mapped the breakpoints of eight chromosome 4 deficiencies relative to the predicted genes along this chromosome. Although the approximate locations of Df(4)G, Df(4)C3, Df(4)M101-62f, Df(4)M101-63a, Df(4)J2, Df(4)O2, Df(4)C1-10AT, and Df(4)B2-2D are known (some from cytological observations and others predicted from P element locations), the extents of these deletions have not been mapped with respect to the predicted genes identified by the Drosophila Genome Project. Polymerase chain reaction primers were designed to amplify the predicted exons of all chromosome 4 genes, and homozygous embryos for each deficiency were identified and their DNA used to test for the presence or absence of these exons. By testing for the inability to amplify various exons along the length of the chromosome, we were able to determine which predicted genes are missing in each deficiency. The five deficiencies, Df(4)G, Df(4)C3, Df(4)C1-10AT, and Df(4)B2-20 (all terminal deletions), and Df(4)M101-62f (a proximal interstitial deletion), enabled us to partition the gene-containing, right arm of chromosome 4 into five regions. Region A [uncovered by Df(4)M101-62f] contains the proximal-most 21 genes; region B [uncovered by Df(4)B2-2D] contains the next 12 genes; region C [uncovered by Df(4)B2-2D and Df(4)C1-10AT] contains the next 17 genes; region D [uncovered by Df(4)B2-2D, Df(4)C1-10AT, and Df(4)C3] contains the next 21 genes; and region E [uncovered by Df(4)B2-2D, Df(4)C1-10AT, Df(4)C3, and Df(4)G] contains the distal-most ten genes. By using Df(4)M101-62f, Df(4)B2-2D, Df(4)C1-10AT, Df(4)C3, and Df(4)G in complementation tests, we can assign newly induced recessive lethal mutations to one of the five regions on chromosome 4. This will substantially reduce the amount of DHPLC analysis required to match each mutation to a predicted transcript on chromosome 4.