Table 1

Phenotypes of COACH subjects with MKS3, RPGRIP1L and CC2D2A mutations

PedigreeMutationsAmino acidAge/sexCNSLiverColRDRenalOther
UW51c.1046T>Cp.L349S21y/MMTS (CT)ELE(18 mo), PH(12y)+AB, ptosis
c.2498T>Cp.I833TBx(1y,12y): BDA, prog CHF
UW54c.675G>Ap.W225X11y/FMTSELE(9y)+LAB, ptosis, small stature
UW56c.515G>Ap.R172Q17y/MMTSELE(10y), PH(15y)+R
c.769A>Gp.M257VBx(12y): BDA, CHF
c.978+3 A>GSplMicropenis
c. 622A>Tp.R208XBx(3y): CHF
UW62c.1115C>Ap.T372K10y/FMTSHSM(6 m)NPHAB
c.1115C>Ap.T372KBx(6 m): BDA, DPM, CHF
c.2322+3 Ins(T)*†Spl
UW63c.2498T>Cp.I833T14y/FMTSBx(14y): BDA, CHF+CRF, NPH, ESRD(13y)AB, anterior anus
c.2498T>Cp.I833TBx(2y): BDA,CHF
UW65c.1321C>Tp.R441C9y/MMTSELE, HSM(11 mo), SM(9y)+Hypogonadism
c.1453C>Tp.P485SBx(11 mo, 9y): BDA, CHF (fig 1C,D)
UW05c.1126C>Gp.Q376E14y/FMTSELE, abn US, PH(13y)+AB
c.1674+3A>G‡SplBx(14y): CHFFetal sibling: MKD
UW30-4c. 1073T>Cp.P358LBirth/FAx: HSM, BDANANAMKDDysmorphic
c. 1911A>Cp.F637Ldec
UW30-3c. 1073T>Cp.P358L1 m/MMTSNA (Ax not done)+−§MKDAB
c. 1911A>Cp.F637Ldec
UW30-5c. 1073T>Cp.P358L18 w/MCVHAx: immature portal fields without evident ductal plate malformationNANAMKDDysmorphic
c. 1911A>Cp.F637LfetusEC
UW83c.1438A>Gp.Y513C8y/FCVHELE(4y)+LAB, ptosis
c.2497T>Cp.I833Tsib: 20 wk M fetus CVH
UW84c.725A>Gp.N242T21y/MMTSHSM(7y), PH, HSP(8y)CRF(16y) Bx(16y): ?NPHPtosis
c.725A>Gp.N242TBx(7y): CHFRx
UW73c.1538A>Gp.Y513C4y/MMTSELE, HSM(3y)familial (paternal) balanced translocation
c.1843T>Cp.C615RBx(4y): BDA, CHF
UW59c.108G>Tp.E361X4y/FMTSELE(1y), Abn US(4y)+AB, ptosis, IM
c.2661+5 G>A*SplBx(3y): CHF
c.2322+3 Ins(T)*†SplBx(5y): CHFSeizures, dystonia
UW52-3c.2802delAp.G934GfsX269y/MMTSELE(18 mo)+R
UW52-4c.2802delAp.G934GfsX264y/MMTSELE, HSM(3y)+MKDAB, ASD/VSD
UW72c.755T>Cp.M252T5y/MMTSELE(4y), abn US(5y)+MKD, CRFAB, small stature, hypothyroid
UW67c.3145 C>Tp.R1049X3y/MMTSELE(2y)EKAB
c.3347 C>Tp.T1116MBx(3y): CHFHTN
UW49**c.3289delGp.V1097FfsX122y/FCVH/ACCHCHSM (5y)+EK, NPHAB, ptosis
c.4582C>Tp.R1528CBx(6, 8, 10y): prog CHF (fig 1E,F)HTN
UW04-3††c.2413C>Tp.R805X17 y/MMTSBx(5y): BDA, CHF (fig 1G,H)EKAB
No mutations
UW66NegativeNegative7.5y/FCVH/ACC (CT)Bx(<1y): CHFAB, abn ears, IM, clubfoot
  • abn, abnormal; AB, abnormal respiratory control; ACC, agenesis of the corpus callosum; AT, cerebellar ataxia; Ax, autopsy; BDA, bile ductule abnormality (proliferation/persistence/dilation) or bile duct dilation on imaging/MRI; Bx, biopsy; C, cirrhotic features including hepatocellular damage/necrosis and evidence of regeneration; CB, cerebellum; CD, choreoathetosis/dystonia; CG, cholangitis; CH, chronic hepatitis; CHF, congenital hepatic fibrosis; CNS, central nervous system; Col, chorioretinal coloboma (bilateral unless otherwise stated); CRF, chronic renal insufficiency; CT, computed tomography scan; CVH, cerebellar vermis hypoplasia; dec, deceased; DPM, ductal plate malformation (classic ring); EC, encephalocele; EK, echogenic kidneys on US; ELE, elevated liver enzymes; ESRD, end stage renal disease; HC, hydrocephalus; HCV, hepatitis C; HD, haemodialysis; HM, hepatomegaly; HR, hyperreflexia; HSM, hepatosplenomegaly; HSP, hypersplenism; IM, intestinal malrotation; LK, large kidneys; MCM, mega cisterna magna; MKD, macrocystic kidney disease; MTS, molar tooth sign on brain MRI; MRI, magnetic resonance imaging; NA, not available/not specified/not known; NC, nephrocalcinosis; NPH, nephronophthisis; PD, polydactyly; PH, portal hypertension (includes complications of PH such as gastrointestinal bleeding/varices); PSS, portosystemic shunt (includes splenorenal, transjugular intrahepatic portosystemic shunts); RD, retinal dystrophy; RMC, renal microcystic disease; Rx, medications; Spl, predicted splicing defect; SZ, seizures; SK, small kidneys; SM, splenomegaly; Tx, transplant; US, ultrasound; V, ventricle(s).

  • All UW subjects had developmental delay/mental retardation, hypotonia and/or ataxia, oculomotor apraxia.

  • Age refers to age at last contact in years (y), months (m) or weeks gestation (w).

  • Laterality of manifestations is stated as either; R, right; L, left; or bilateral unless otherwise stated.

  • Outcome details are italicised and appear in the lower portion of the cell.

  • * Not seen in >192 control chromosomes.

  • splicing of exon 22 was not affected in a lymphoblastoid cell line from UW58.

  • results in the use of a cryptic splice within intron 16 and a premature termination codon one amino acid after exon 16.

  • § fundus flavus noted on retinal exam.

  • predicted to be benign by Polyphen and SIFT (see text).

  • ** previously published in Gorden et al (2008).

  • †† brother without liver disease is listed in table 2.