Spectrum of genetic alterations in patients with peroxisome biogenesis defects in the Iranian population: a case series study

Khalilian, Sheyda; Fathi, Mohadeseh; Jamshidi, Sanaz; Madannejad, Rasoul; Sayad, Arezou; Ghafouri-Fard, Soudeh; Miryounesi, Mohammad

doi:10.1186/s12920-025-02126-3

Table 1 Summary of clinical and molecular findings in patients with peroxisomal disorders

From: Spectrum of genetic alterations in patients with peroxisome biogenesis defects in the Iranian population: a case series study

Case number	Gene	Transcript	Variant	Associated disease	OMIM	Inheritance	Zygosity	dbSNP rsID	Clinvar*	ACMG classification*	Frequency in gnome AD	Frequency in Iranome	Age	Sex	Consanguinity	Indication	Ref
1	PEX1	NM_000466.3	c.2528G > A p.Gly843Asp	Peroxisome biogenesis disorder 1 A (Zellweger) & 1B	214,100 601,539	AR	Hom	rs61750420	Pathogenic	Pathogenic	0.062%	No observation	1 year	M	N	history of asphyxia, seizure from age of 5 months, hepatomegaly, developmental delay and pallor of optic disk	[15, 16]
2	PEX1	NM_000466.2	c.2876G > C p.Arg959Pro	Heimler syndrome 1 Peroxisome biogenesis disorder 1 A /1B (Zellweger)	234,580 214,100 601,539	AR	Hom	rs773206107	Likely Pathogenic	VUS	0.0%	No observation	8 years	M	N	abnormal gait, progressive spasticity, incontinence and normal metabolic test
3	PEX1	NM_000466.3	c.2528G > A p.Gly843Asp	Heimler syndrome 1 Peroxisome biogenesis disorder 1 A (Zellweger) Peroxisome biogenesis disorder 1B (NALD/IRD)	234,580 214,100 601,539	AR AR AR	Het	rs61750420	Pathogenic	Pathogenic	0.062%	No observation	6 months	F	N	microcephaly, hypotonia, respiratory distress, and hearing loss	[15, 16]
3	PEX1	NM_000466.3	c.1136_1140del p.Glu379Glyfs*12		234,580 214,100 601,539	AR AR AR	Het	-	Pathogenic	Likely Pathogenic	0.0%	No observation	6 months	F	N
4	PEX1	NM_000466.3	c.2528G > A p.Gly843Asp	Heimler syndrome 1 Peroxisome biogenesis disorder 1 A (Zellweger) Peroxisome biogenesis disorder 1B (NALD/IRD)	234,580 214,100 601,539	AR	Het	rs61750420	Pathogenic	Pathogenic	0.062%	No observation	16 months	F	N	hypotonia, elevated liver enzyme, strabismus and retinal disorder	[15, 16]
4	PEX1	NM_000466.3	c.313 C > T p.Gln105*		234,580 214,100 601,539	AR	Het	-	Likely Pathogenic	NR	0.0%	No observation	16 months	F	N		NR
5	PEX1	NM_000466.2	c.2783 + 6T > C	Heimler syndrome 1 Peroxisome biogenesis disorder 1 A (Zellweger)/ 1B(NALD/IRD)	234,580 214,100 601,539	AR	Hom	rs1585224298	VUS	VUS	0.0%	No observation	9 years	M	Y	seizure at 8 months, motor delay, hearing loss, developmental delay
6	PEX5	NM_000319.5	c.1775 C > T p.Pro592Leu	Peroxisome biogenesis disorder 2 A (Zellweger) Peroxisome biogenesis disorder 2B Rhizomelic chondrodysplasia punctata, type 5	214,110 202,370 616,716	AR AR AR	Hom	rs748956654	Likely Pathogenic	Conflict	0.0%	No observation	5 years	M	Y	motor delay	[17]
6	ATL3	NM_015459.5	c.16 C > T p.Arg6*	Neuropathy, hereditary sensory, type IF	615,632	AD	Het	rs1455374554	Likely Pathogenic	VUS	0.0%	No observation	5 years	M	Y	motor delay	[18]
7	PEX6	NM_000287	c.2626 C > T p.Arg876Trp	Heimler syndrome 2 Peroxisome biogenesis disorder 4 A Peroxisome biogenesis disorder 4B	616,617 614,862 614,863	AR	Hom	rs267608246	Likely Pathogenic	VUS	< 0.0001%	No observation	31 years	F	Y	hearing loss, visual impairment, and MR	[19, 20]
8	PEX7	NM_000288	c.946 C > T p.Pro316Ser	Rhizomelic chondrodysplasia punctata, type 1 Peroxisome biogenesis disorder 9B	215,100 614,879	AR AR	Hom	rs746310299	VUS	VUS	0.003%	No observation	1.5 years	M	N	developmental delay, hypotonia and hearing loss
9	PEX7	NM_000288	c.257G > A p.Cys86Tyr	Peroxisome biogenesis disorder 9B Rhizomelic chondrodysplasia punctata, type 1	614,879 215,100	AR	Hom	-	Likely Pathogenic	Likely Pathogenic	0.0%	0.06%	1 year	F	Y	developmental delay, cataract, rhizomelic extremities and clinical diagnosis of Rhizomelic chondrodysplasia punctata	[21,22,23]
10	PEX12	NM_000286	c.959 C > T p.Ser320Phe	Peroxisomal Biogenesis Disorder 3	601,758 614,859	AR	Hom	rs28936697	Pathogenic	Pathogenic	< 0.001%	No observation	5 years	M	N	developmental delay, seizure, motor retardation, nystagmus and hearing loss	[24]
11	PEX12	NM_000286.3	c.625 C > T p.Gln209Ter	Peroxisome biogenesis disorder 3 A (Zellweger) Peroxisome biogenesis disorder 3B	614,859 266,510	AR	Hom	rs61752106	Pathogenic	Pathogenic	0.02%	No observation	5 months	F	Y	seizure, hypotonia, ASD, hearing loss, and agenesis of cerebellar vermis and corpus callosum in brain MRI	[25]
12	PEX12	NM_000286	c.204_206delTCT p.Leu68del	Peroxisome biogenesis disorder 3 A (Zellweger) and 3B	614,859 266,510	AR	Hom	rs61752098	VUS	VUS	0.0%	No observation	6 months	F	Y	severe hypotonia, hearing loss, intractable seizures, developmental delay and Sleep Apnea	[26]
13	ACOX1	NM_004035.7	c.961 A > T p.Ile321Phe	Peroxisomal acyl-CoA oxidase deficiency	264,470	AR	Hom	-	VUS	NR	0.0%	No observation	4 years	F	Y	hypotonia, developmental delay, aphasia and right partial polygyria in brain MRI	NR
13	KIF5C	NM_004522	c.1666 A > T p.Lys556*	Cortical dysplasia, complex, with other brain malformations	615,282	AD	Het	-	VUS	NR	0.0%	No observation	4 years	F	Y
14	ACOX1	NM_004035	c.1478 + 1G > A	Peroxisomal acyl-CoA oxidase deficiency	264,470	AR	Hom	-	Likely Pathogenic	Likely Pathogenic	0.0%	No observation	7 years	F	Y	history of developmental regression

AR: autosomal recessive, Hom: homozygote, Het: heterozygote, VUS: Variant of uncertain significance, NR: not reported; M: male, F: female, Y: yes, N: No
*ACMG/Clinvar classification criteria: pathogenic, likely pathogenic, Variant of uncertain significance, likely benign, and benign

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