Identification of Critical Region Responsible for Split Hand/Foot Malformation Type 3 (SHFM3) Phenotype through Systematic Review of Literature and Mapping of Breakpoints Using Microarray Data.
Split hand/foot malformation (SHFM) is a limb malformation with underdeveloped or absent central digital rays, clefts of hands and feet, and variable syndactyly of the remaining digits. There are six types of SHFM. Here, we report a boy with SHFM type 3 having normal 4th and 5th digits, absent 2nd and 3rd digits, and a 4th finger flexion deformity, as well as absent 2nd, 3rd and 4th toes bilaterally. His father, two paternal uncles, and two paternal first cousins have similar phenotype. Chromosome analysis showed a normal male karyotype. A 514 kb gain at 10q24.31-q24.32 (chr10:102,962,134-103,476,346, hg19) was identified using 6.0 Single nucleotide polymorphism (SNP) microarray, resulting in the duplication of nine genes, including BTRC and FBXW4. A detailed systematic review of literature and mapping of breakpoints using microarray data from all reported cases in PubMed and DECIPHER were conducted, and exon 1 of BTRC gene was identified as the critical region responsible for the SHFM3 phenotype. The potential mechanism and future studies of this critical region causing the SHFM3 phenotype are discussed.
Center for Human Genetics, Cambridge, MA 02139, USA. cli@chginc.org.
Catherine F
CF
Li
Center for Human Genetics, Cambridge, MA 02139, USA. kangione@chginc.org.
Katie
K
Angione
Center for Human Genetics, Cambridge, MA 02139, USA. jmilunsky@chginc.org.
Jeff M
JM
Milunsky
10q24.31–q24.32; BTRC; FBXW4; Split hand/foot Malformation (SHFM3); duplication