TY - JOUR
T1 - Deletion of a 760 kb region at 4p16 determines the prenatal and postnatal growth retardation characteristic of Wolf-Hirschhorn syndrome
AU - Concolino, Daniela
AU - Rossi, Elena
AU - Strisciuglio, Pietro
AU - Iembo, Maria Antonietta
AU - Giorda, Roberto
AU - Ciccone, Roberto
AU - Tenconi, Romano
AU - Zuffardi, Orsetta
PY - 2007/10
Y1 - 2007/10
N2 - 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.
AB - 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.
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U2 - 10.1136/jmg.2007.050963
DO - 10.1136/jmg.2007.050963
M3 - Article
C2 - 17911656
AN - SCOPUS:35348891957
VL - 44
SP - 647
EP - 650
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
SN - 0022-2593
IS - 10
ER -