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Glycosylphosphatidylinositol biosynthesis defect 25(GPIBD25)

MedGen UID:: 1823964
•Concept ID:: C5774191
•: Disease or Syndrome

Synonyms:	GPIBD25; NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA AND CONTRACTURES

Gene (location): Gene(s) directly associated with this condition or phenotype.	C18orf32 (18q21.1)

Monarch Initiative:	MONDO:0859271
OMIM®:	619985

Definition

Glycosylphosphatidylinositol biosynthesis defect-25 (GPIBD25) is an autosomal recessive neurodevelopmental disorder characterized by global developmental delay, brain anomalies, hypotonia, and contractures (Salian et al., 2022). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293). [from OMIM]

Clinical features

From HPO

Ankle flexion contracture

MedGen UID:: 332440
•Concept ID:: C1837407
•: Anatomical Abnormality

See: Feature record | Search on this feature

Short stature

MedGen UID:: 87607
•Concept ID:: C0349588
•: Finding

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

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Severe global developmental delay

MedGen UID:: 332436
•Concept ID:: C1837397
•: Finding

A severe delay in the achievement of motor or mental milestones in the domains of development of a child.

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Delayed CNS myelination

MedGen UID:: 867393
•Concept ID:: C4021758
•: Anatomical Abnormality

Delayed myelination in the central nervous system.

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Hypotonia

MedGen UID:: 10133
•Concept ID:: C0026827
•: Finding

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

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Low alkaline phosphatase

MedGen UID:: 349734
•Concept ID:: C1860130
•: Finding

Abnormally reduced serum levels of alkaline phosphatase.

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Coarse hair

MedGen UID:: 124454
•Concept ID:: C0277959
•: Finding

Hair shafts are rough in texture.

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Sparse hair

MedGen UID:: 1790211
•Concept ID:: C5551005
•: Finding

Reduced density of hairs.

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Inversion of nipple

MedGen UID:: 82844
•Concept ID:: C0269269
•: Anatomical Abnormality

The presence of nipples that instead of pointing outward are retracted inwards.

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Abnormality of limbs
- Ankle flexion contracture
Abnormality of metabolism/homeostasis
- Low alkaline phosphatase
Abnormality of the breast
- Inversion of nipple
Abnormality of the integument
- Coarse hair
- Sparse hair
Abnormality of the musculoskeletal system
- Hypotonia
Abnormality of the nervous system
- Delayed CNS myelination
- Severe global developmental delay
Growth abnormality
- Short stature

Recent clinical studies

Etiology

The immunologic abnormalities in patients with paroxysmal nocturnal hemoglobinuria are associated with disease progression.

Wang G, Che M, Zeng L, Liu H, Li L, Liu Z, Fu R
Saudi Med J 2024 Apr;45(4):424-432. doi: 10.15537/smj.2024.45.4.20231010. PMID: 38657993 Free PMC Article

Significantly different clinical phenotypes associated with mutations in synthesis and transamidase+remodeling glycosylphosphatidylinositol (GPI)-anchor biosynthesis genes.

Carmody LC, Blau H, Danis D, Zhang XA, Gourdine JP, Vasilevsky N, Krawitz P, Thompson MD, Robinson PN
Orphanet J Rare Dis 2020 Feb 4;15(1):40. doi: 10.1186/s13023-020-1313-0. PMID: 32019583 Free PMC Article

Sphingolipids from the human fungal pathogen Aspergillus fumigatus.

Fontaine T
Biochimie 2017 Oct;141:9-15. Epub 2017 Jun 23 doi: 10.1016/j.biochi.2017.06.012. PMID: 28652019

High incidence of transiently appearing complement-sensitive bone marrow precursor cells in patients with severe aplastic anemia--A possible role of high endogenous IL-2 in their suppression.

Nissen C, Tichelli A, Gratwohl A, Warthmann C, Moser Y, dalle Carbonare V, Sendelov S, Chklovskaia E, Jansen W, Wodnar-Filipowicz A, Sadallah S, Speck B
Acta Haematol 1999;101(4):165-72. doi: 10.1159/000040948. PMID: 10436296

Genotypic, immunophenotypic and clinical features of Thai patients with paroxysmal nocturnal haemoglobinuria.

Pramoonjago P, Pakdeesuwan K, Siripanyaphinyo U, Chinprasertsuk S, Kinoshita T, Wanachiwanawin W
Br J Haematol 1999 May;105(2):497-504. PMID: 10233427

See all (6)

Diagnosis

Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ: Report of seven new subjects and review of the literature.

Johnstone DL, Nguyen TTM, Zambonin J, Kernohan KD, St-Denis A, Baratang NV, Hartley T, Geraghty MT, Richer J, Majewski J, Bareke E, Guerin A, Pendziwiat M, Pena LDM, Braakman HMH, Gripp KW, Edmondson AC, He M, Spillmann RC, Eklund EA, Bayat A, McMillan HJ, Boycott KM, Campeau PM
J Inherit Metab Dis 2020 Nov;43(6):1321-1332. Epub 2020 Aug 3 doi: 10.1002/jimd.12278. PMID: 32588908 Free PMC Article

A post glycosylphosphatidylinositol (GPI) attachment to proteins, type 2 (PGAP2) variant identified in Mabry syndrome index cases: Molecular genetics of the prototypical inherited GPI disorder.

Thompson MD, Knaus AA, Barshop BA, Caliebe A, Muhle H, Nguyen TTM, Baratang NV, Kinoshita T, Percy ME, Campeau PM, Murakami Y, Cole DE, Krawitz PM, Mabry CC
Eur J Med Genet 2020 Apr;63(4):103822. Epub 2019 Dec 2 doi: 10.1016/j.ejmg.2019.103822. PMID: 31805394

Cerebral visual impairment and intellectual disability caused by PGAP1 variants.

Bosch DG, Boonstra FN, Kinoshita T, Jhangiani S, de Ligt J, Cremers FP, Lupski JR, Murakami Y, de Vries BB
Eur J Hum Genet 2015 Dec;23(12):1689-93. Epub 2015 Mar 25 doi: 10.1038/ejhg.2015.42. PMID: 25804403 Free PMC Article

A novel iron uptake mechanism mediated by GPI-anchored human p97.

Kennard ML, Richardson DR, Gabathuler R, Ponka P, Jefferies WA
EMBO J 1995 Sep 1;14(17):4178-86. doi: 10.1002/j.1460-2075.1995.tb00091.x. PMID: 7556058 Free PMC Article

Characterization of the complement sensitivity of calcium loaded human erythrocytes.

Test ST, Bütikofer P, Yee MC, Kuypers FA, Lubin B
Blood 1991 Dec 1;78(11):3056-65. PMID: 1720041

See all (8)

Therapy

High incidence of transiently appearing complement-sensitive bone marrow precursor cells in patients with severe aplastic anemia--A possible role of high endogenous IL-2 in their suppression.

Emergence of CD52-, glycosylphosphatidylinositol-anchor-deficient lymphocytes in rheumatoid arthritis patients following Campath-1H treatment.

Brett SJ, Baxter G, Cooper H, Rowan W, Regan T, Tite J, Rapson N
Int Immunol 1996 Mar;8(3):325-34. doi: 10.1093/intimm/8.3.325. PMID: 8671618

See all (2)

Prognosis

Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ: Report of seven new subjects and review of the literature.

See all (1)

Clinical prediction guides

The immunologic abnormalities in patients with paroxysmal nocturnal hemoglobinuria are associated with disease progression.

Wang G, Che M, Zeng L, Liu H, Li L, Liu Z, Fu R
Saudi Med J 2024 Apr;45(4):424-432. doi: 10.15537/smj.2024.45.4.20231010. PMID: 38657993 Free PMC Article

Early infantile epileptic encephalopathy due to biallelic pathogenic variants in PIGQ: Report of seven new subjects and review of the literature.

Analysis of exome data for 4293 trios suggests GPI-anchor biogenesis defects are a rare cause of developmental disorders.

Pagnamenta AT, Murakami Y, Taylor JM, Anzilotti C, Howard MF, Miller V, Johnson DS, Tadros S, Mansour S, Temple IK, Firth R, Rosser E, Harrison RE, Kerr B, Popitsch N; DDD Study, Kinoshita T, Taylor JC, Kini U
Eur J Hum Genet 2017 Jun;25(6):669-679. Epub 2017 Mar 22 doi: 10.1038/ejhg.2017.32. PMID: 28327575 Free PMC Article

High incidence of transiently appearing complement-sensitive bone marrow precursor cells in patients with severe aplastic anemia--A possible role of high endogenous IL-2 in their suppression.

Characterization of the complement sensitivity of calcium loaded human erythrocytes.

Test ST, Bütikofer P, Yee MC, Kuypers FA, Lubin B
Blood 1991 Dec 1;78(11):3056-65. PMID: 1720041

See all (7)

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Glycosylphosphatidylinositol biosynthesis defect 25(GPIBD25)

Definition

Clinical features

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

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