Proximal 19q trisomy: a new syndrome of morbid obesity and mental retardation.
ABSTRACT To report on the clinical and metabolic characteristic and the unique chromosomal defect of a mentally retarded and morbidly obese patient.
A 13-year follow-up, including insulin sensitivity, lipid profile and polysomnography studies and various therapeutic interventions are described. The presence of a supernumerary marker in karyotype preparation was further studied by fluorescence in situ hybridization (FISH). Comparative genomic hybridization (CGH) was used to identify the source of the chromosomal marker.
Insulin resistance was found by the homeostatic model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). M-FISH identified euchromatin derived from chromosome 19, and CGH confirmed the FISH results and demonstrated that the supernumerary marker derived from 19q12 to 19q13.2.
The clinical and metabolic characteristics in association with partial chromosomal trisomy differ our patient from the currently known syndromes of obesity and mental retardation. The metabolic impairments in this case can derive from unbalanced expression of several genes in the 19q12-19q13.2 region, genes that are related to adipose tissue homeostasis and insulin resistance. The clinical and genetic similarities to a previously reported case may suggest that partial 19q trisomy is a new syndrome of obesity and mental retardation.
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ABSTRACT: Free fatty acids are the major source of fuel for mammals, and hormone sensitive lipase (LIPE) plays a critical role in lipid metabolism by mobilizing free fatty acids from stored triglycerides. We have identified and sequenced a partial cDNA for LIPE. Cosmids were identified by hybridization and mapped to 19q13.1-->q13.2 by FISH. Direct sequence analysis of a 1 kb segment of cosmid 26710 identifies a dinucleotide repeat in an intron upstream of exon 8 of human LIPE. This marker was heterozygous 82% of the time with 12 alleles (166-190 bp) detected in 122 chromosomes. The most likely order for this gene is: qter-[D19S178/LIPE]-(3 cM)-D19S47-(1 cM)-D19S190-RYR1-cen.Cytogenetics and cell genetics 01/1995; 69(3-4):211-4.
Article: Distal 19q duplication.[show abstract] [hide abstract]
ABSTRACT: Two brothers with a distal 19q duplication due to a maternal balanced reciprocal translocation were observed. Clinical features included intrauterine and postnatal growth retardation, microcephaly, and mental retardation with seizures. Dysmorphic facies consisted of coarse hair with a high frontal hairline, short philtrum and nose, flat nasal root, and a broad mouth with downturned commissures. Both routine G-banded and high-resolution prometaphase chromosome studies were employed in evaluation of the family. The dysmorphic features and karyotypes of the affected brothers are compared with those of the two previously reported families with 19q duplication, and a common distal-19q phenotype is suggested.Human Genetics 02/1982; 60(3):267-70. · 4.63 Impact Factor
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ABSTRACT: We describe our experience in the molecular diagnosis of 22 patients suspected of Prader Willi syndrome (PWS) using a DNA probe PW71 (D15S63) which detects a parent-of-origin specific methylated site in the PWS critical region. The cause of the syndrome was determined as deletion or uniparental disomy according to the segregation of (CA)n dinucleotide repeat polymorphisms of the PWS/AS region and more distal markers of chromosome 15. In 10 patients the clinical diagnosis was confirmed by this approach, 6 with paternal deletion and 4 with maternal disomy. In one patient, the aberrant methylation pattern that was detected by PW71 could not be confirmed by the segregation of (CA)n, probably due to paternal microdeletion in the PWS critical region which did not include the loci D15S97, D15S113, GABRB3, and GABRA5. This case demonstrates the advantage of the DNA probe PW71 in the diagnosis of PWS. © 1994 Wiley-Liss, Inc.American Journal of Medical Genetics 07/1994; 52(1):79 - 84.