Furthermore we confirm the overlap of acro-renal-ocular syndrome with Okihiro syndrome at the molecular level and expand the phenotype of SALL4 mutations.
This finding illustrates that the phenotypic and functional effects of SALL4 missense mutations are difficult to predict, and that other SALL4 missense mutations might lead to phenotypes not overlapping with Okihiro syndrome.
SALL4 mutations may also cause acro-renal-ocular syndrome (AROS), which differs from DRRS by the presence of structural eye anomalies, and phenotypes similar to thalidomide embryopathy and Holt-Oram syndrome (HOS).
Furthermore, we demonstrated that anorectal and heart anomalies in Okihiro syndrome are caused by Sall4 haploinsufficiency and that Sall4/Sall1 heterozygotes exhibited an increased incidence of anorectal and heart anomalies, exencephaly and kidney agenesis.
This finding illustrates that the phenotypic and functional effects of SALL4 missense mutations are difficult to predict, and that other SALL4 missense mutations might lead to phenotypes not overlapping with Okihiro syndrome.
This finding illustrates that the phenotypic and functional effects of SALL4 missense mutations are difficult to predict, and that other SALL4 missense mutations might lead to phenotypes not overlapping with Okihiro syndrome.
Prominent expression in the developing midbrain, branchial arches and the limbs suggests an important function of SALL4 during development of these structures as expected from the observation in Okihiro syndrome patients.
Here we report the detection and molecular characterization of four novel, overlapping microdeletions, all spanning SALL4 and flanking genes, in four unrelated cases with features of Okihiro syndrome and variable degrees of psychomotor delay.
Furthermore we confirm the overlap of acro-renal-ocular syndrome with Okihiro syndrome at the molecular level and expand the phenotype of SALL4 mutations.
Notably, previous studies demonstrated the genetic involvement of SALL4 loss-of-function variants in Okihiro syndrome and related syndromic developmental disorders.
The authors examined four male and two female affected members of a pedigree previously reported to cosegregate DRRS and a heterozygous SALL4 mutation.
SALL4 mutations may also cause acro-renal-ocular syndrome (AROS), which differs from DRRS by the presence of structural eye anomalies, and phenotypes similar to thalidomide embryopathy and Holt-Oram syndrome (HOS).