title: Refinement of the Region for Split Hand/Foot Malformation 5 on 2q31.1.
abstract: Background: Deletions that encompass 2q31.1 have been proposed as a microdeletion syndrome with common clinical features, including intellectual disability/developmental delay, microcephaly, cleft palate, growth delay, and hand/foot anomalies. In addition, several genes within this region have been proposed as candidates for split hand-foot malformation 5 (SHFM5). Methods: To delineate the genotype-phenotype correlation between deletions of this region, we identified 14 individuals with deletions at 2q31.1 detected by microarray analysis for physical and developmental disabilities. Results: All subjects for whom detailed clinical records were available had neurological deficits of varying degree. Seven subjects with deletions encompassing the HOXD cluster had hand/foot anomalies of varying severity, including syndactyly, brachydactyly, and ectrodactyly. Of 7 subjects with deletions proximal to the HOXD cluster, 5 of which encompassed DLX1/DLX2, none had clinically significant hand/foot anomalies. In contrast to previous reports, the individuals in our study did not display a characteristic gestalt of dysmorphic facial features. Conclusion: The absence of hand/foot anomalies in any of the individuals with deletions of DLX1/DLX2 but not the HOXD cluster supports the hypothesis that haploinsufficiency of the HOXD cluster, rather than DLX1/DLX2, accounts for the skeletal abnormalities in subjects with 2q31.1 microdeletions.
authors.affiliation: Signature Genomic Laboratories, Spokane, Wash.
authors.forename: A
authors.initials: A
authors.lastname: Theisen
authors.forename: J A
authors.initials: JA
authors.lastname: Rosenfeld
authors.forename: K
authors.initials: K
authors.lastname: Shane
authors.forename: K L
authors.initials: KL
authors.lastname: McBride
authors.forename: J F
authors.initials: JF
authors.lastname: Atkin
authors.forename: C
authors.initials: C
authors.lastname: Gaba
authors.forename: J
authors.initials: J
authors.lastname: Hoo
authors.forename: T W
authors.initials: TW
authors.lastname: Kurczynski
authors.forename: R E
authors.initials: RE
authors.lastname: Schnur
authors.forename: L B
authors.initials: LB
authors.lastname: Coffey
authors.forename: E H
authors.initials: EH
authors.lastname: Zackai
authors.forename: L
authors.initials: L
authors.lastname: Schimmenti
authors.forename: N
authors.initials: N
authors.lastname: Friedman
authors.forename: M
authors.initials: M
authors.lastname: Zabukovec
authors.forename: S
authors.initials: S
authors.lastname: Ball
authors.forename: R
authors.initials: R
authors.lastname: Pagon
authors.forename: A
authors.initials: A
authors.lastname: Lucas
authors.forename: C K
authors.initials: CK
authors.lastname: Brasington
authors.forename: J E
authors.initials: JE
authors.lastname: Spence
authors.forename: S
authors.initials: S
authors.lastname: Sparks
authors.forename: V
authors.initials: V
authors.lastname: Banks
authors.forename: W
authors.initials: W
authors.lastname: Smith
authors.forename: T
authors.initials: T
authors.lastname: Friedberg
authors.forename: P R
authors.initials: PR
authors.lastname: Wyatt
authors.forename: M
authors.initials: M
authors.lastname: Aust
authors.forename: R
authors.initials: R
authors.lastname: Tervo
authors.forename: A
authors.initials: A
authors.lastname: Crowley
authors.forename: D
authors.initials: D
authors.lastname: Skidmore
authors.forename: A N
authors.initials: AN
authors.lastname: Lamb
authors.forename: B
authors.initials: B
authors.lastname: Ravnan
authors.forename: T
authors.initials: T
authors.lastname: Sahoo
authors.forename: R
authors.initials: R
authors.lastname: Schultz
authors.forename: B S
authors.initials: BS
authors.lastname: Torchia
authors.forename: M
authors.initials: M
authors.lastname: Sgro
authors.forename: D
authors.initials: D
authors.lastname: Chitayat
authors.forename: L G
authors.initials: LG
authors.lastname: Shaffer