De Pontual et al. (2011) studied 2 female probands with skeletal abnormalities consistent with a diagnosis of Feingold syndrome: microcephaly, short stature, and digital abnormalities including brachydactyly, brachymesophalangy of the second and fifth fingers, hypoplastic thumbs of variable ... De Pontual et al. (2011) studied 2 female probands with skeletal abnormalities consistent with a diagnosis of Feingold syndrome: microcephaly, short stature, and digital abnormalities including brachydactyly, brachymesophalangy of the second and fifth fingers, hypoplastic thumbs of variable severity, and cutaneous syndactyly of the toes. Both probands had mild mental retardation. Their fathers were similarly affected, and 1 of the probands had an affected sister.
De Pontual et al. (2011) performed high-resolution CGH arrays in 10 probands with skeletal abnormalities consistent with a diagnosis of Feingold syndrome (see 164280) but who lacked any mutation at the MYCN gene (164840), and in 2 of ... De Pontual et al. (2011) performed high-resolution CGH arrays in 10 probands with skeletal abnormalities consistent with a diagnosis of Feingold syndrome (see 164280) but who lacked any mutation at the MYCN gene (164840), and in 2 of the probands they identified germline hemizygous microdeletions at chromosome 13q31.3 that segregated with disease in both families. The deletion in the first patient spanned 2.89 Mb and encompassed 3 genes, LOC144776, MIR17HG (609415), and GPC5 (602446), whereas the deletion in the second patient spanned 165 kb and encompassed only MIR17HG and the first exon of GPC5. By searching the DECIPHER database (Firth et al., 2009), which contained array CGH data from more than 6,000 individuals with a variety of disorders, they identified a third proband who had a 180-kb hemizygous 13q31.3 microdeletion encompassing the entire MIR17HG gene and the first exon of GPC5. The third patient was not classified as having Feingold syndrome, but displayed a combination of features compatible with the diagnosis. Quantitative RT-PCR on total RNA of white blood cells from the 3 deletion-positive probands showed that expression of all 6 miRNAs encoded by MIR17HG was approximately 50% relative to that of controls. De Pontual et al. (2011) noted that whereas some predicted loss-of-function variants in GPC5 were listed in databases of genomes of healthy individuals, they identified no structural variants or polymorphisms directly affecting the miRNAs encoded by the miR17-92 cluster in those databases. In addition, mice harboring targeted deletion of the Mir17-92 cluster displayed a phenocopy of several key features of the human syndrome (see ANIMAL MODEL). De Pontual et al. (2011) stated that this was the first example of a miRNA gene responsible for a syndromic developmental defect in humans. The authors noted that none of the 3 individuals with a MIR17HG deletion had gastrointestinal atresia, leaving open the question of whether they represented true cases of Feingold syndrome or a new form of brachydactyly with short stature and microcephaly.