Mosaic maternal uniparental isodisomy for chromosome 7q21-qter

• Published in: Clinical genetics 2006-09, Vol.70 (3), p.207-213
• Main Authors: Reboul, M-P, Tandonnet, O, Biteau, N, Belet-de Putter, C, Rebouissoux, L, Moradkhani, K, Vu, PY, Saura, R, Arveiler, B, Lacombe, D, Taine, L, Iron, A
• Format: Article
• Language: English
• Subjects: Alleles; Biological and medical sciences; CFTR gene mutation; Child, Preschool; Chlorides - analysis; Chromosomes, Human, Pair 7 - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Fetal Growth Retardation - genetics; General aspects. Genetic counseling; Genomic Imprinting - genetics; growth retardation; Humans; In Situ Hybridization, Fluorescence; Infant, Newborn; Infant, Small for Gestational Age; Male; Medical genetics; Medical sciences; microsatellite markers; Microsatellite Repeats - genetics; Mosaicism; Polymorphism, Single Nucleotide; Recombination, Genetic; Sweat - chemistry; Uniparental Disomy - diagnosis; Uniparental Disomy - genetics; uniparental isodisomy
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2006.00664.x

Uniparental disomy (UPD) for several human chromosomes is associated with clinical abnormalities. We report the case of a 2‐year‐old boy with severe intrauterine and post‐natal growth retardation (IUGR/PNGR) and highly variable sweat chloride concentrations. The patient was identified as heterozygous for the F508del mutation of the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Unexpectedly, the signal corresponding to the maternally inherited F508del allele appeared much more intense than the paternally derived wild allele. Molecular analysis including polymorphic marker studies, microsatellites and single‐nucleotide polymorphisms subsequently showed that the boy was a carrier of a de novo mosaic maternal isodisomy of a chromosome 7 segment while there was a biparental inheritance of the rest of the chromosome. This is the first report of a mosaic partial UPD7. The matUPD7 segment at 7q21‐qter extends for 72.7 Mb. The karyotype (550 bands) of our patient was normal, and fluorescence in situ hybridization with probes mapping around the CFTR gene allowed us to rule out a partial duplication. The detection of this chromosomal rearrangement confirms the hypothesis that the 7q31‐qter segment is a candidate for the localization of human imprinted genes involved in the control of IUGR and PNGR. It also emphasizes the importance of searching for UPD7 in severe, isolated and unexplained IUGR and PNGR.