Anisomastia associated with interstitial duplication of chromosome 16, mental retardation, obesity, dysmorphic facies, and digital anomalies : Molecular mapping of a new syndrome by fluorescent in situ hybridization and microsatellites to 16q13 (D16S419-D16S503)

• Published in: The journal of clinical endocrinology and metabolism Vol. 85; no. 9; pp. 3396 - 3401
• Main Authors: STRATAKIS, Constantine A, LAFFERTY, Antony, TAYMANS, Susan E, GAFNI, Rachel I, MECK, Jeanne M, BLANCATO, Jan
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.09.2000
• Subjects: Adult; Biological and medical sciences; Breast - abnormalities; Chromosome aberrations; Chromosomes, Human, Pair 16 - genetics; DNA - genetics; DNA - isolation & purification; DNA Probes; Face - abnormalities; Female; Fingers - abnormalities; Gene Duplication; Humans; In Situ Hybridization, Fluorescence; Intellectual Disability - genetics; Karyotyping; Medical genetics; Medical sciences; Microsatellite Repeats - genetics; Obesity - genetics; Chromosomal aberration; Breast disease; Diseases of the osteoarticular system; Developmental disorder; Dysmorphic facies; Mental retardation; Genetic determinism; Disease of the hand; Adult; Female; Chromosome 16; Nutritional status; Human; Obesity; Nutrition disorder; Case study; Concomitant disease; Asymmetry; Malformation; Clinodactyly; Cytogenetics; Intellectual deficiency; Abnormal chromosome; Chromosome duplication; Karyotype
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.85.9.3396

Anisomastia is a common problem among developing adolescent girls. We recently evaluated a 22-yr-old female patient who had severe anisomastia (which had been repaired by surgery), associated with moderate to severe mental retardation, a stocky body habitus with mild obesity, dysmorphic facies (prominent, upslanting palpebral fissures, beaked nose, and a prominent philtrum), webbed neck, low hairline, and severe bilateral clinodactyly of the third, fourth, and fifth fingers with acral (but not large joint) flexion contractures. A peripheral blood high resolution karyotype revealed additional chromosomal material within the long arm of chromosome 16. Densitometric analysis of amplified polymorphic sequence-tagged sites (STS) mapping to 16q suggested that the duplication is defined by the noninvolved markers D16S419 [16q12-cen, 66 centimorgan (cM) from 16p terminus] and D16S421 (16q13-q21, 84.4 cM), encompassing a maximum of 18.4 cM of genetic distance. The STS analysis showed that the duplication was on the maternally derived chromosome 16, resulting in two maternal (and one paternal) copies of that region of chromosome 16. The location was further confirmed by bacterial artificial chromosomes (BACs) that were obtained from a commercially available library, labeled, and used for fluorescence in situ hybridization. The BACs containing STSs D16S408, D16S3137, and D16S3032 (markers that correspond to 16q13) showed two regions of hybridization, indicating that these sites were duplicated, whereas a BAC containing the STS D16S512 (which corresponds to 16q21-q22) revealed one hybridization signal per 16q, indicating that the corresponding region was not involved in the duplication. The distance between the probe signals suggested a tandem duplication. We conclude that even though trisomy 16 is the most common autosomal trisomy in spontaneous abortions, few patients with unbalanced chromosome 16 abnormalities survive to adulthood; in this report we describe one such patient with an interstitial chromosome 16 duplication (at 16q13), who had a specific phenotype associated with abnormal breast size. There are clinical similarities between this patient and patients with other 16q abnormalities, although the breast findings were unique. Molecular cytogenetics, including fluorescence in situ hybridization and densitometric analysis of amplified STSs, provided useful tools for the precise mapping of the syndrome to 16q13, where the gene(s) responsible for this phenotype might be localized.