Ann Haskins Olney

Publications (7)17.53 Total impact

• Article: Characterization of six novel patients with MECP2 duplications due to unbalanced rearrangements of the X chromosome.

  Jennifer N Sanmann, Danielle L Bishay, Lois J Starr, Carla A Bell, Diane L Pickering, Jadd M Stevens, Stephen G Kahler, Ann Haskins Olney, G Bradley Schaefer, Warren G Sanger
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  ABSTRACT: Males with duplication of the Xq28 region, including methyl CpG-binding protein 2 (MECP2), exhibit a characteristic phenotype, including developmental delay, intellectual disability, limited or absent speech, limited or absent ambulation, and recurrent respiratory infections. We report six males with MECP2 duplications identified using array comparative genomic hybridization. The minimal sizes of these duplications range from ∼0.08 to 14.13 Mb, which, to the best of our knowledge, are respectively the smallest and largest minimal size duplications molecularly characterized to date. Adjunct metaphase fluorescence in situ hybridization analysis further classified these duplications as tandem or as products of complex chromosomal rearrangements. Specifically, one complex rearrangement was described as a der(12)t(X;12)(q28;q24.33), which is the first report of a translocation involving MECP2 on Xq and chromosome 12. The other complex rearrangement was described as a rec(X)dup(Xq)inv(X)(p22.32q28)mat. Synthesis of the dysmorphic features identified in individuals with rec(X) chromosomes, including deletions in the pseudoautosomal region 1 (PAR1) at Xp22.33/Yp11.3 and duplications of the distal Xq region including MECP2, revealed a high prevalence of undescended testes (7/8) and micropenis (3/8) in this cohort. Given that micropenis is rare in the general population, but present in 38% of individuals in this cohort, a dosage anomaly at one or both loci may be a significant risk factor for this condition. Therefore, we recommend microarray testing for patients with unexplained micropenis, particularly when accompanied by other phenotypic anomalies.
  American Journal of Medical Genetics Part A 05/2012; 158A(6):1285-91. · 2.39 Impact Factor
• Article: 18q22.3 --> 18q23 deletion syndrome and cleft palate.

  James D Eudy, Diane L Pickering, Richard Lutz, Kristal Platt, Bhavana J Dave, Ann Haskins Olney, Warren G Sanger
  American Journal of Medical Genetics Part A 04/2010; 152A(4):1046-8. · 2.39 Impact Factor
• Article: Inherited 14q duplication and 21q deletion: A rare adjacent‐2 segregation in multiple family members

  Bhavana J. Dave, Ann Haskins Olney, Dianna H. Zaleski, Diane L. Pickering, Troy A. Becker, Hope E. Chipman, Warren G. Sanger
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  ABSTRACT: We present a family with multiple carriers of a subtle balanced translocation t(14;21)(q21.2;q21.2) and three patients with a resultant adjacent-2 malsegregation containing a +der(14)t(14;21)(q21.2;q21.2),-21 in their chromosome complement. The initial study was performed when a 2-month-old female was referred to genetics clinic for evaluation of developmental delay, growth retardation, and failure to thrive. Physical findings included prominent eyes, micrognathia, prominent and simple external ears, camptodactyly, contractures of the wrists, ankles, and hips, hypoplasia of the corpus callosum, prominent atria and occipital horns, cerebellopontine hypoplasia; and small atrial septal defect. High resolution chromosomes showed an extra band on the proximal 21q and fluorescence in situ hybridization (FISH) demonstrated only one signal for the centromere of 21. Karyotypes of the parents and grandparents revealed that the mother and maternal grandfather were carriers of a balanced translocation, and the propositus contained an unbalanced chromosome complement with partial duplication of proximal 14q and partial deletion of proximal 21q. Investigations performed on an institutionalized maternal aunt revealed identical karyotypic abnormalities as in the propositus. More recently, array comparative genomic hybridization (aCGH) on a subsequent child with multiple congenital anomalies further out in the extended family allowed for more accurate identification of the breakpoints. Our investigation includes analysis on a total of 11 family members spanning three generations. Among those investigated, there were no living members with other possible consequential unbalanced translocations or with adjacent-2 segregation resulting in −14,+der(21). Chromosome rearrangements require FISH and aCGH studies for accurate identification and elucidation of the abnormality and breakpoints. © 2009 Wiley-Liss, Inc.
  American Journal of Medical Genetics Part A 09/2009; 149A(10):2248 - 2253. · 2.39 Impact Factor
• Article: Inherited 14q duplication and 21q deletion: a rare adjacent-2 segregation in multiple family members.

  Bhavana J Dave, Ann Haskins Olney, Dianna H Zaleski, Diane L Pickering, Troy A Becker, Hope E Chipman, Warren G Sanger
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  ABSTRACT: We present a family with multiple carriers of a subtle balanced translocation t(14;21)(q21.2;q21.2) and three patients with a resultant adjacent-2 malsegregation containing a +der(14)t(14;21)(q21.2;q21.2),-21 in their chromosome complement. The initial study was performed when a 2-month-old female was referred to genetics clinic for evaluation of developmental delay, growth retardation, and failure to thrive. Physical findings included prominent eyes, micrognathia, prominent and simple external ears, camptodactyly, contractures of the wrists, ankles, and hips, hypoplasia of the corpus callosum, prominent atria and occipital horns, cerebellopontine hypoplasia; and small atrial septal defect. High resolution chromosomes showed an extra band on the proximal 21q and fluorescence in situ hybridization (FISH) demonstrated only one signal for the centromere of 21. Karyotypes of the parents and grandparents revealed that the mother and maternal grandfather were carriers of a balanced translocation, and the propositus contained an unbalanced chromosome complement with partial duplication of proximal 14q and partial deletion of proximal 21q. Investigations performed on an institutionalized maternal aunt revealed identical karyotypic abnormalities as in the propositus. More recently, array comparative genomic hybridization (aCGH) on a subsequent child with multiple congenital anomalies further out in the extended family allowed for more accurate identification of the breakpoints. Our investigation includes analysis on a total of 11 family members spanning three generations. Among those investigated, there were no living members with other possible consequential unbalanced translocations or with adjacent-2 segregation resulting in -14,+der(21). Chromosome rearrangements require FISH and aCGH studies for accurate identification and elucidation of the abnormality and breakpoints.
  American Journal of Medical Genetics Part A 09/2009; 149A(10):2248-53. · 2.39 Impact Factor
• Article: Array-based comparative genomic hybridization analysis of 1176 consecutive clinical genetics investigations.

  Diane L Pickering, James D Eudy, Ann Haskins Olney, Bhavana J Dave, Denae Golden, Jadd Stevens, Warren G Sanger
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  ABSTRACT: Cytogenetic investigations are useful for etiologic determinations of mental retardation, developmental delay, multiple congenital anomalies, and pregnancy complications; however, the causes remain elusive in a majority of cases despite high-resolution cytogenetic studies and multiple fluorescence in situ hybridization examinations. Array-based comparative genomic hybridization has the ability to examine the genome at a higher resolution and may yield an increased detection of genetic abnormalities. The purpose of this study was to assess the use of array-based comparative genomic hybridization in a clinical genetics setting. DNA from 1176 patients was analyzed using a bacterial artificial chromosome array-based comparative genomic hybridization platform. All abnormal cases were confirmed by fluorescence in situ hybridization and parental studies were completed when possible. Of the 1176 patients included in this survey, 163 showed a genomic imbalance identified by array-based comparative genomic hybridization. Of these 163 cases, 116 had a clinically relevant genetic abnormality. A total of 9.8% (116 of 1176 cases) were determined to exhibit a causative genomic imbalance. Twenty-five of the 116 abnormal cases had a previously identified cytogenetic abnormality yielding an increased detection rate of 7.9% (91 of 1146) in cases with normal or no cytogenetics. Array-based comparative genomic hybridization increases the overall abnormality detection rate, thus improving the diagnostic potential of clinical cytogenetics investigations.
  Genetics in medicine: official journal of the American College of Medical Genetics 05/2008; 10(4):262-6. · 3.92 Impact Factor
• Article: Macrocephaly syndromes.

  Ann Haskins Olney
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  ABSTRACT: Anatomic megalencephaly resulting in macrocephaly occurs in more than 100 multiple congenital anomaly syndromes. A number of macrocephaly syndromes show accompanying somatic overgrowth, but some show normal somatic growth. This discussion provides a review of several macrocephaly syndromes that might be encountered by the pediatric neurologist. Growth patterns, craniofacial features, congenital anomalies, central nervous system imaging findings, performance, and mode of inheritance for each condition are reviewed as well as recent developments in the molecular genetic testing for these conditions.
  Seminars in Pediatric Neurology 10/2007; 14(3):128-35. · 1.65 Impact Factor
• Article: Cryptic duplication and deletion of 9q34.3 --> qter in a family with a t(9;22)(q34.3;p11.2).

  Travis M Sanger, Ann Haskins Olney, Dianna Zaleski, Diane Pickering, Marilu Nelson, Warren G Sanger, Bhavana J Dave
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  ABSTRACT: A newborn male was referred for genetic evaluation because of multiple congenital abnormalities. Physical findings included a round face, telecanthus, hypertelorism, a short upturned nose with anteverted nares, small ears, micrognathia, short toes, and congenital heart disease. Chromosome analysis detected a possible deletion of 9qter because of satellite material on 9qter. Delineation by FISH and microarray CGH studies showed 46,XY,der(9)t(9;22)(q34.3;p11.2). The mother and maternal grandfather had a balanced t(9;22)(q34.3;p11.2) rearrangement. Also, the maternal great-aunt of the propositus was found to have a duplication of 9q34.3 --> qter. FISH was required to delineate her karyotype, which was 46,XX.ish der(22)t(9;22)(q34.3;p11.2). This maternal great-aunt and one of her daughters (cytogenetics not done) have a relatively normal phenotype, only reporting mild learning disabilities in school. Since the 22p material involved in this rearrangement is clinically irrelevant, this report describes an individual with a pure deletion of 9q34.3 --> qter and another with a pure duplication of 9q34.3 --> qter.
  American Journal of Medical Genetics Part A 10/2005; 138(1):51-5. · 2.39 Impact Factor