Fig. 1

Clinical and molecular findings of the patient. a Facial features, i.e., light blue sclerae, wide forehead, flat face, sparse scalp hair, narrow mouth (i), skin hyperextensibility on the neck and dorsum of the hand (ii, iii), single palmar crease and laxity of the thumb (iv), laxity of the fifth finger (v), small atrophic scar on knee (vi), low-set thumb and clinodactyly of the fifth finger (vii), disproportionate short stature, hypotonia and edema of the lower limbs (viii, ix), pes planus and hallux valgus (x). b Absence of radioulnar synostosis (i-iii), osteopenia and absence of metaphyseal flaring (iv), metatarsophalangeal subluxation and severe hallux valgus (v). c Sequence chromatograms showing the position of the homozygous B4GALT7 c.829G>T variant (arrow) (seq. Ref.: NM_007255.2, NP_009186.1) (i). RT-PCR with a primer pair encompassing exons 4–6 performed on total RNA from patient’s blood demonstrated that the c.829G>T transversion, which affects the first nucleotide of exon 6, impacts splicing (ii). In particular, apart from the usage of the wild type acceptor (allele 1), an alternative acceptor 3 bp downstream (allele 2), and the presence of a splice product with retention of intron 5 (allele 3) were disclosed (iii). These different alleles should lead to a truncated protein (p.Glu277*), in-frame deletion (p.Glu277del), and insertion of 10 amino acids followed by a stop codon (p.Glu276_Glu277ins11*), respectively