BACKGROUND: Recently the genotype/phenotype map of Wolf-Hirschhorn syndrome (WHS) has been refined, using small 4p deletions covering or flanking the critical region in patients showing only some of the WHS malformations. Accordingly, prenatal-onset growth retardation and failure to thrive have been found to result from haploinsufficiency for a 4p gene located between 0.4 and 1.3 Mb, whereas microcephaly results from haploinsufficiency of at least two different 4p regions, one of 2.2-2.38 Mb and a second one of 1.9-1.28 Mb. METHODS AND RESULTS: We defined the deletion size of a ring chromosome (r(4)) in a girl with prenatal onset growth retardation, severe failure to thrive and true microcephaly but without the WHS facial gestalt and mental retardation. A high-resolution comparative genome hybridisation array revealed a 760 kb 4p terminal deletion. CONCLUSIONS: This case, together with a familial 4p deletion involving the distal 400 kb reported in normal women, may narrow the critical region for short stature on 4p to 360-760 kb. This region is also likely to contain a gene for microcephaly. "In silico" analysis of all genes within the critical region failed to reveal any strikingly suggestive expression pattern; all genes remain candidates for short stature and microcephaly.
BACKGROUND: Recently the genotype/phenotype map of Wolf-Hirschhorn syndrome (WHS) has been refined, using small 4p deletions covering or flanking the critical region in patients showing only some of the WHS malformations. Accordingly, prenatal-onset growth retardation and failure to thrive have been found to result from haploinsufficiency for a 4p gene located between 0.4 and 1.3 Mb, whereas microcephaly results from haploinsufficiency of at least two different 4p regions, one of 2.2-2.38 Mb and a second one of 1.9-1.28 Mb. METHODS AND RESULTS: We defined the deletion size of a ring chromosome (r(4)) in a girl with prenatal onset growth retardation, severe failure to thrive and true microcephaly but without the WHS facial gestalt and mental retardation. A high-resolution comparative genome hybridisation array revealed a 760 kb 4p terminal deletion. CONCLUSIONS: This case, together with a familial 4p deletion involving the distal 400 kb reported in normal women, may narrow the critical region for short stature on 4p to 360-760 kb. This region is also likely to contain a gene for microcephaly. "In silico" analysis of all genes within the critical region failed to reveal any strikingly suggestive expression pattern; all genes remain candidates for short stature and microcephaly.
Authors: G Van Buggenhout; C Melotte; B Dutta; G Froyen; P Van Hummelen; P Marynen; G Matthijs; T de Ravel; K Devriendt; J P Fryns; J R Vermeesch Journal: J Med Genet Date: 2004-09 Impact factor: 6.318
Authors: Georges Boog; Claudine Le Vaillant; Michel Collet; Pierre François Dupré; Philippe Parent; André Bongain; Bernard Benoit; Claire Trastour Journal: Fetal Diagn Ther Date: 2004 Sep-Oct Impact factor: 2.587
Authors: N Tommerup; L Aagaard; C L Lund; E Boel; S Baxendale; G P Bates; H Lehrach; H Vissing Journal: Hum Mol Genet Date: 1993-10 Impact factor: 6.150
Authors: César Paz-Y-Miño; Ana Proaño; Stella D Verdezoto; Juan Luis García; Jesús María Hernández-Rivas; Paola E Leone Journal: BMC Med Genomics Date: 2019-11-21 Impact factor: 3.063