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Table 1 Studies describing the 17p13.3 duplication/ triplications associated with SHFM or SHFLD

From: Split hand/foot malformation with long bone deficiency associated with BHLHA9 gene duplication: a case report and review of literature

Reference [No.] No. of families/ individuals with duplication/ triplication (a) Limb anomalies of affected individuals Extra-limb manifestations Special remarks
ezirovitz et al., 2008 [3] 1 family
9 affected individuals
SHFM (4), SHFLD [tibial hemimelia] (3), Tibial hemimelia/aplasia only (2) No Autosomal dominant (AD) inheritance/ Variable expressivity (VE)/, Incomplete penetrance (IP),
Defined candidate region to 17p13.1 – 17p13.3; ~ 861 kb
Armour et al., 2011 [4] 3 families (?1 with triplicationa) with 12 affected individuals
7 with duplication: 6 affected, 1 unaffected
Split hand only (3),
SHFLD [tibial hypoplasia/aplasia] (9)
No AD inheritance/ VE/ IP
Defined critical region of ~ 173 kb, ?BHLHA9 or AC016292 duplication
Klopocki et al., 2011 [5] 17 families (out of 56)
82 with duplication: 42 affected, 40 unaffected
SHFLD [tibial hemimelia] (18/31)
Only SHFM (5)
No AD inheritance/ VE/ IP
Sex bias: (Male>Female), affected females with more severe phenotype
Defined critical region of ~ 11.8 kb
encompassing only BHLHA9 gene
Petit et al., 2013 [7] 2 affected with duplication Case 1 SHFLD [R/radial agenesis and hypoplastic R/ulna and L/radial hypoplasia]
Case 2 SHFM only
Case 1 small ASD Involvement of radius reported for the first time
Curry et al., 2013 [8] 1 affected
14 families in this report (total of 21 families analyzed) with 17p13.3 duplications that includes BHLHA9
SHFLD [tibial hemimelia] Cleft palate, Mild ID  
Luk et al., 2014 [9] 1 affected fetusa
Unaffected mothera
both with duplication
Split hands No First case with prenatal genetic diagnosis
Petit et al., 2014 [10] 13 families with 42 affected individuals and 19 unaffected obligate carriers;
29 with the duplication (20 affected, 9 unaffected)
SHFLD (18) No AD inheritance/ VE/ IP
Involvement of radius in 2 individuals
Femur hypoplasia in one patient
Affected males with more severe phenotype
Al Kaissi et al., 2014 [11] 1 affected
Father- bilateral partial syndactyly
SHFM, tibial hemimelia Sacral hypoplasia, DD, Thrombocyto-penia  
Nagata et al., 2014 [12] 27 families
64 with the duplication/triplication (42/42 affected patients, 22/47 unaffected relatives);
2/1000 Japanese controls positive for duplication
SHFM (29), SHFLD (11), GWC (2) NR No sex bias
SHFLD and GWC more common in triplications
Nagata et al., 2015 [13] 1 affected childa
Unaffected mothera
both with triplication
SHFM with tibial aplasia (R)/ hypoplasia (L) and wide R/ distal femoral metaphysis (GWC-like malformation) No  
Cho et al., 2015 [14] 1 affected fetus
with the duplication
SHFLD, campomelia of R/femur, Bilateral agenesis of fibula, bilateral club feet, oligosyndactyly No  
Fusco et al., 2017 [15] 3 affected
with the duplication
SHFLD; tibial hypoplasia (2)
One with isolated tibial hypoplasia
One with ASD  
Shen et al., 2018 [16] 1 family with 5 affected individuals, 4 affected fetuses
10 tested (8 individuals, 2 fetuses)
8 with the duplication; 6 affected, 2 unaffected
SFFM (4)
SHFLD (1), bilateral femoral hypoplasia
Present report
1 affected child
Affected mother
SHFM (?with tibial hemimelia) No  
  1. ASD Atrial septal defect, DD Developmental delay, GWC Goellop Woolfgang Complex, ID Intellectual disability, R Right, L Left
  2. aIndividuals with 17p13.3 triplication