Deletion of a 760 kb region at 4p16 determines the prenatal and postnatal growth retardation characteristic of Wolf-Hirschhorn syndrome.
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.


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.
Concolino
Daniela
D
Rossi
Elena
E
Strisciuglio
Pietro
P
Iembo
Maria Antonietta
MA
Giorda
Roberto
R
Ciccone
Roberto
R
Tenconi
Romano
R
Zuffardi
Orsetta
O
D002675:Child, Preschool; D002894:Chromosomes, Human, Pair 4; D003582:Cytogenetics; D002658:Developmental Disabilities / Q000235:genetics*; D019066:Facies; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008831:Microcephaly / Q000235:genetics*; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D013577:Syndrome