Table 1.

IFT172 Mutations in 14 Individuals from 12 Families Affected by Skeletal Ciliopathies, ATD and MZSDS

Individuala	Ethnic Origin	Nucleotide Mutationb	Deduced Protein Alteration	Exon or Intron (Zygosity, Segregation)	Amino Acid Evolutionary Conservation	PolyPhen-2 (HumVar)	MutationTaster	Parental Consanguinity	Clinical Diagnosis	Skeletal Features	Renal Disease (ESRD)	Other Clinical Features
NPH2218	Hungarian	c.432delA	p.Lys144Asnfs∗15	6 (het, p)	-	-	-	no	ATD, JBTS	TD, SS, SLB	NPHP (6 years)	RD, LF, OMA, CVH, ID, obesity
		c.4161G>Ac	p.Arg1387Serfs∗7	38 (het, m)	-	-	-
A3189-21	Pakistani	c.886C>Td	p.Arg296Trp	9 (hom)	D. melanogaster	0.967	DC	yes	MZSDS	SS	NPHP (9 years)	RD, ID, died at 12 years
UCL-87	Turkish	c.1232T>A	p.Ile411Asn	13 (hom) (het, p/m)	D. melanogaster	0.890	DC	yes	ATD	TD, TA, PD (feet)	none (−)	LF, died at 18 months
UCL-107	Turkish	c.1232T>A	p.Ile411Asn	13 (hom)	D. melanogaster	0.890	DC	yes	ATD	TD, TA	none (−)	LF, died at 3 months
NPH2161	French	c.1390_1395delGATATT	p.Asp464_Ile465 del	14 (het)	D. melanogaster and D. rerio	-	-	ND	MZSDS	BD	NPHP (34 years)	RD, cholestasis
		c.5179T>Ce	p.Cys1727Arg	48 (het)	D. rerio	0.648	DC
B1	Belgian	c.1671_1672dupAG	p.Val558Glufs∗12	16 (het, p)	-	-	-	no	ATD	TD, TA, PSCE, BD, PD	none (−)	RD, ID
		c.5179T>Ce	p.Cys1727Arg	48 (het, m)	D. rerio	0.648	DC
SKDP-44.3	British	c.2158delC	p.Arg720Valfs∗28	21 (het, m)	-	-	-	no	ATD	TD, TA, SS, BD	mild structural abnormalities	RD, cholestasis, OMA, ID, obesity
		c.5179T>Ce	p.Cys1727Arg	48 (het, p)	D. rerio	0.648	DC
A3215-21	South American	c.2716C>T	p.Gln906∗	25 (het, m)	-	-	-	no	ATD	TD, SS, GV	NPHP (12 years), RTX (13 years)	ID
		c.4607T>C	p.Leu1536Pro	42 (het, p)	C. reinhardtii	0.807	DC
F108-21	German	c.3228+1G>A	5′ splice site	29 (het, m)	-	-	-	no	MZSDS	PCSE, BD	NPHP (11 years)	RD, LF, IGT, obesity
		c.4607T>C	p.Leu1536Pro	42 (het, p)	C. reinhardtii	0.807	DC
SKDP-165.3	Singaporean and Malaysian	c.3907C>T	p.Arg1303∗	35 (het, p)	-	-	-	no	ATD	TD, TA, PD, SLB	early cystic dysplasia	LF, VSD, hydrocephalus, died by induced abortion
		c.4630C>T	p.Arg1544Cys	42 (het, m)	D. melanogaster	0.991	DC
A2052-21 and A2052-22	Filipino	c.4630C>T	p.Arg1544Cys	42 (hom) (het, p/m)	D. melanogaster	0.991	DC	yes	ATD, MZSDS, JBTS	TD, TA, PCSE, BD	NPHP (2 years), RTX (4 years)	RD, LF, OMA, CVH, ID
A3037-21 and A3037-22	European American	c.4925_4928del GAGA	p.Arg1642Lysfs∗32	46 (het, p)	-	-	-	no	MZSDS	PCSE, BD	NPHP (20 years)	RD, LF, obesity
		c.5179T>Ce	p.Cys1727Arg	48 (het, m)	D. rerio	0.648	DC

Abbreviations are as follows: BD, brachydactyly; ESRD, end-stage renal disease; CVH, cerebellar vermis hypoplasia; DC, predicted to be “disease causing”; GV, genu valgum; het, heterozygous; hom, homozygous; ID, intellectual disability; IGT, impaired glucose tolerance; ATD, asphyxiating thoracic dystrophy; JBTS, Joubert syndrome; LF, liver fibrosis; m, maternal; MZSDS, Mainzer-Saldino syndrome; ND, no data; NPHP, nephronophthisis; OMA, ocular motor apraxia; p, paternal; PD, polydactyly; PCSE, phalangeal cone-shaped epiphysis; RD, retinal degeneration; RTX, renal transplantation; SLB, short long bone; SS, short stature; TA, trident acetabulum; TD, thoracic dystrophy (small bell-shaped thorax); and VSD, ventriculoseptal defect.

^aIn sibling cases, clinical information refers to the underlined individual.

^bcDNA mutations are numbered according to human cDNA RefSeq NM_015662.1 (IFT172); +1 corresponds to the A of the ATG start translation codon.

^cThis variant abrogates the 3′ splice site (Figure S2). It is in 1000 Genomes (its minor allele frequency is not annotated), but not in the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project Exome Variant Server (EVS).

^dNHLBI EVS (n = 6,503 control subjects): T/T = 0; T/C = 1; C/C = 6,502.

^eNHLBI EVS (n = 6,503 control subjects): C/C = 0; C/T = 1; T/T = 6,502.