Table 1 COQ2 variants and phenotypes published in the literature

Diomedi-Camassei et al. [9]

c.[437G > A];[437G > A]

p.[(Ser146Asn)];[(Ser146Asn)]

Acute renal failure, epileptic encephalopathy, hypotonia; died at 6 months

N/A

Severe multisystem

Mollet et al. [12]

c.[1197delT];[1197delT]

p.[(Asn401Ilefs*15)];[(Asn401

Ilefs*15)]

Neurological distress at birth; liver failure and nephrotic syndrome at 2 days; died at day 12 from multi-organ failure

N/A

Severe multisystem

Jakobs et al. [11]

c.[905C > T];[905C > T]

p.[(Ala302Val)];[(Ala302Val)]

Dizygotic twins; Premature birth, feeding problems, generalized edema, seizures, apnea; retinopathy of prematurity in one twin; infantile death

N/A

Severe multisystem

Scalais et al. [13]

c.[326G > A];[326G > A]

p.[(Ser109Asn)];[(Ser109Asn)]

Myoclonic seizures, HCM, hypotonia, nystagmus (10 weeks);nephrotic syndrome (4 mo); died at 5 months

No improvement and continued deterioration

Severe multisystem

Dinwiddie et al. [8]

c.437G > A(;)1159C > T

p.(Ser146Asn)(;)(Arg387Ter)

Additional c.3754C > A variant in the MT-ND1 gene

Neonatal diabetes, HCM, cardiomegaly, metabolic acidosis, encephalopathy, chronic renal tubular disease, respiratory failure, died at 2 months

N/A

Severe multisystem

Desbats et al. [7]

c.[545 T > G];[545 T > G]

p.[(Met182Arg)];[(Met182Arg)]

Lactic acidosis, proteinuria, hepatic insufficiency, dilation of left ventricle, worsening neurological condition, died at 23 h

N/A

Severe multisystem

Eroglu et al. [10]

c.[437G > A];[437G > A]

p.[(Ser146Asn)];[(Ser146Asn)]

Index case in family; neonatal diabetes, glomerular proteinuria, seizures, encephalopathy, hypotonia, electroretinography showed no response, death at 4.5 months

No improvement of renal or neurological symptoms

Severe multisystem

Eroglu et al. [10]

c.[437G > A];[437G > A]

p.[(Ser146Asn)];[(Ser146Asn)]

Affected sibling; neonatal diabetes, proteinuria, mild metabolic acidosis, seizures, kidney failure, died due to multi-organ failure at 31 months

Normalization of glucose, lactate levels; neurological deterioration with encephalopathy and refractory seizures; deterioration of kidney function

Severe multisystem

Eroglu et al. [10]

c.[437G > A];[437G > A]

p.[(Ser146Asn)];[(Ser146Asn)]

Index case in family; vomiting, proteinuria, nephrotic syndrome, refractory seizures, died at 6 months

N/A

Severe multisystem

Eroglu et al. [10]

c.[437G > A];[437G > A]

p.[(Ser146Asn)];[(Ser146Asn)]

Affected sibling; neonatal diabetes, proteinuria, seizures, diffuse cerebral atrophy; died at 14 months

Proteinuria improved; continued neurological deterioration

Severe multisystem

Xu et al. [23]

c.[518G > A];[973A > G]

p.[(Arg173His)];[(Thr325Ala)]

Edema, mild motor delay, moderate speech delay, nephrotic syndrome (11 months)

Edema resolved; improved kidney and motor development

NS + neurological symptoms

Quinzii et al. [19], Salviati et al. [20], Diomedi-Camassei et al. [9], Lopez-Martin [16], Montini et al. [18]

c.[890A > G];[890A > G]

p.[(Tyr297Cys)];[(Tyr297Cys)]

Index case in family; epileptic encephalopathy, hypotonia, mild psychomotor delay, optic atrophy, nephropathy, rod-cone retinopathy (11 mo), kidney transplant (3 years)

Drastic improvement in neurological manifestations; no improvement in renal dysfunction

NS + neurological symptoms + RP

Quinzii et al. [19], Salviati et al. [20], Diomedi-Camassei et al. [9], Lopez-Martin [16], Montini et al. [18]

c.[890A > G];[890A > G]

p.[(Tyr297Cys)];[(Tyr297Cys)]

Sister affected with only nephrotic syndrome (12 mo); no extra-renal involvement

Resolution of nephrotic syndrome

Isolated NS

Diomedi-Camassei et al. [9]

c.[590G > A];[683A > G]

p.[(Arg197His)];[(Asn228Ser)]

Nephrotic syndrome (onset at 18 mo); no extrarenal involvement

Neurological examination continued to be normal after 8-mo of follow up

Isolated NS

McCarthy et al. [17]

c.[683A > G];[701delT]

p.[(Asn228Ser)];[(Leu234Argfs*14)]

Nephrosis, renal failure (2 years)

N/A

Isolated NS

Bezdicka et al. [14]

c.[683A > G];[683A > G]

p.[(Asn228Ser)];[(Asn228Ser)]

Two affected siblings; nephrotic syndrome (3 years)

Kidney function improved in sibling; no supplementation in index case

Isolated NS

Starr et al. [21]

c.[973A > G];[1159C > T]

p.[(Thr325Ala)];[(Arg387Ter)]

Nephrotic syndrome (9 months)

Nephrotic syndrome resolved; continued proteinuria

Isolated NS

Starr et al. [21]

c.[176dupT];[683A > G]

p.[(Ala69Argfs*33)]; [(Asn228Ser)]

Nephrotic syndrome (2 years)

Nephrotic syndrome resolved; continued proteinuria

Isolated NS

Wu et al. [22]

c.[832 T > C];[832 T > C]

p.[(Cys278Arg)];[(Cys278Arg)]

Also homozygous c.1213 + 1G > A variant in ARSB gene

Nephrotic syndrome, died (6 mo); no extrarenal involvement

N/A

Isolated NS

Starr et al. [21]

c.[683A > G];[881C > T]

p.[(Asn228Ser)];[(Thr294Ile)]

Nephrotic syndrome (10 years)

Nephrotic syndrome not resolved, progressed to ESRD

Juvenile-onset NS

Gigante et al. [15]

c.[1169G > C];[1169G > C]

p.[(Gly390Ala)];[(Gly390Ala)]

Index case in family with juvenile onset nephrotic syndrome and myoclonic epilepsy (16 years); affected cousin also with juvenile onset nephrotic syndrome (16 years), and headaches associated with phono-and photophobia

N/A

Juvenile-onset NS + neurological symptoms

Hara et al. [24], Mitsui et al. [25]

c.[382A > G];[382A > G]

p.[(Met128Val)];[(Met128Val)]

Additionally homozygous p.(Val393Ala) variant in COQ2 also detected

Index case in family; multi-system atrophy (onset 68 years), RP (diagnosed at 33 years)

N/A

MSA + RP

Hara et al. [24], Mitsui et al. [25]

c.[382A > G];[382A > G]

p.[(Met128Val)];[(Met128Val)]

Additionally homozygous p.(Val393Ala) variant in COQ2 also detected

Affected sibling; multi-system atrophy (onset 62 years),RP(diagnosed at 51 years)

N/A

MSA + RP

Current study

c.[288dupC];[376C > G]

p.[(Ala97Argfs*56)]; [(Arg126Gly)]

Three affected siblings with renal abnormalities and RP

No improvement in ERG function

NS + RP