Human Genetic Disorders and Knockout Mice Deficient in Glycosaminoglycan

Table 1

Transporters for UDP-sugars and sulfate as well as biosynthetic enzymes for PAPS.

Transporters and enzymes	Coding genes; (synonym)	Chromosomal location	mRNA accession number	MIM number	Human genetic disorders	Clinical features	References for the human diseases	References for the knockout mice
Solute carrier family 26 member A2; (diastrophic dysplasia sulfate transporter)	SLC26A2 (DTDST)	5q31–q34	NM_000112	600972; 256050; 222600; 226900	Achondrogenesis type IB Atelosteogenesis type II Diastrophic dysplasia Multiple epiphyseal dysplasia autosomal recessive type	Lethal chondrodysplasia with severe under-development of skeleton, extreme micromelia, death before or immediately after birth.; Epiphyseal dysplasia and early onset osteoarthritis.	[38–40]	[41]
Solute carrier family 35 member D1 (UDP-GlcUA/UDP-GalNAc dual transporter)	SLC35D1 (UGTrel7)	1p32-p31	NM_015139	269250	Schneckenbecken; dysplasia	Neonatal lethal chondrodysplasia, platyspondyly with oval-shaped vertebral bodies, extremely short long bones with dumbbell-like appearance, and small ilia with snail-like appearance.	[42]	[42]
PAPS synthase 2	PAPSS2	10q24	NM_004670; NM_001015880	612847	Spondyloepimetaphyseal dysplasia Pakistani type (PAPSS2 type) Hyperandrogenism Brachyolmia autosomal recessive type	Short, bowed lower limbs, enlarged knee joint, kyphoscoliosis, and mild generalized brachydactyly.; Androgen excess, premature pubarche, hyperandrogenic anovulation, low level of serum, dehydroepiandrosterone,; short trunk, kyphosis, and scoliosis.	[43–48]	[22, 23, 49–53]
3′-Phosphoadenosine 5′-phosphate; 3′-phosphatase	IMPAD1 (PAPP)	8q12.1	NM_017813	614078; 614010	Chondrodysplasia with joint dislocations GPAPP type	Short stature, chondrodysplasia, with brachydactyly, congenital joint dislocations, cleft palate, and facial dysmorphism.	[54]	[55]

MIM: mendelian inheritance in man.
Among the several transporters and biosynthetic enzymes involved in PAPS and UDP-sugars, some of the mutations that occur have been shown to cause human genetic disorders and are listed here.