| Objective Finger (toe) abnormality is one of common genetic defects, which includes large-area defect of four limbs, subtle change of the number, length and structure of anatomic form of finger (toe). Usually, it is an autosomal dominantly inherited disease. It also can be an autosomal recessive disorder sometimes. Finger (toe) abnormality includes Synpolydactyly(SPD), split-hand/split-foot malformation(SHFM) and Brachydactyly (BD). We have collected two families with finger (toe) abnormality in order to identify the genetic mutation, with the clear understanding of which we can provide services on genetic counseling and fertility guidance for the patients and their family members.Methods We collected the peripheral blood from21members (10patients) of family Ⅰ and2members (patients) of family Ⅱ and extracted their gDNA. We screened HOXD13and TP63, which were the hot genes of phalangeal anomalies by PCR-sequencing in the probands in family Ⅰ and family Ⅱ. Having not been detected any genetic abnormality,20members from the predigree Ⅰ were analyzed genome-widely with500K genome-wide gene chips from Affymetrix company. The result of gene-chip-analysis was verified by using real-time PCR.Results①Form the result of gene chips, a duplication was found, at the chromosome10q24.3of all patients from predigree Ⅰ, while not found in normal members. The max duplication size was6.06Mb (102,836,500-103,442,636), while the minimum one was2Mb (102,987,572-103,187,708). The result of real-time PCR testing indicated that the duplication region included FKSG40、TLX1、LBX1、 BTRC、POLL and FBXW4.②A heterozygous mutation was found in TP63in two patients from family II, which leaded to an amino changed (Tyrosine to Systeine) at CDS192.Conclusion We made definite molecular diagnosis in two families with Finger (toe) abnormality. A duplication in the chromosome10q24.3was found in all patients from family I. And a heretozygous missense mutation, Tyr129Cys, was found in patients from family Ⅱ. |
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