Examples of human disorders caused by the defects in vesicular trafficking machinery
| Human disorder (inheritance, OMIM number) | Gene | Type of IDT | Phenotype | |||
|---|---|---|---|---|---|---|
| Hypo-pigmentation | Neuro-developmental abnormalities/ neuropathy | Disturbed immune function | Major features | |||
| AD, autosomal dominant; AR, autosomal recessive; CSCA, defects in cytoskeletal and cytoskeleton-associated proteins; CSVB, defects in cargo selection and vesicle biogenesis; RAR, defects in Rabs and Rab-associated proteins, VTF, defects in vesicle tethering and fusion. | ||||||
| Congenital disorder of glycosylation type IIe (AR, 608779) | COG7 | CRVB | – | + | + | Liver disease, cardiac failure, death in infancy, recurrent infections |
| Factor V and Factor VIII coagulation factor deficiency (AR, 601567 and 227300) | LMAN1 (ERGIC-53); MCFD2 | CRVB | – | – | – | Haemophilia due to combined clotting factors V and VIII deficiency |
| Hermansky–Pudlak syndrome (AR, 604982, 606118, 606682, 607521, 607522, 608233, 603401, 607145, 609762) | ADTB3A, HPS-1, HPS3-6, DTNBP1 | CRVB | + | + | + | Patients with HPS1 and HPS4 mutations may have pulmonary fibrosis and colitis |
| Chediak–Higashi syndrome (AR, 214500) | LYST/CHS1 | CRVB | + | – | + | Neutropenia, lymphomas and neurological abnormalities in adulthood |
| Cranio–lenticulo–sutural dysplasia (AR, 607812) | SEC23A | CRVB | – | – | – | Delayed ossification of cranial bones, hyperpigmentation, cataracts |
| Choroideraemia (XL, 300390) | REP1 | RAR | – | + | – | Degeneration of retinal pigment epithelium and photoreceptors of the eye, atrophy of the retina and choroid, progressive loss of vision beginning at an early age |
| Mental retardation (XL, 300104) | RABGDIA | RAR | – | + | – | Non-specific mental retardation; carrier female patients may also be mildly affected |
| Warburg Micro syndrome and Martsolf syndrome (AR, 600118 and 212720) | RAB3GAP | RAR | – | + | – | Cataracts, microphthalmia, microcephaly, microgenitalia |
| Bardet–Biedl syndrome, BBS3 (AR, 209900) | ARL6 | RAR/CRVB | – | + | – | Renal cysts, small stature, mental retardation, retinopathy, cardiac malformations, hypogenitalism |
| Griscelli syndrome type I (Elajalde syndrome) (AR, 214450) | MYO5A (Myosin VA) | RAR/CSCA | + | + | – | Primary neurological impairment |
| Griscelli syndrome type II (AR, 607624) | RAB27A | RAR/CSCA | + | + | + | T lymphocyte and macrophage activation syndrome; may have secondary neurological impairment |
| Griscelli syndrome type III (AR, 609227) | MLPH | RAR/CSCA | + | – | – | Purely a pigmentation disorder |
| Charcot–Marie–Tooth disease 2b (hereditary motor and sensory neuropathy type IIB) (AD, 608882) | RAB7 | RAR/CSCA | – | + | – | Late-onset distal muscle weakness, wasting, foot ulcers and infections |
| Charcot–Marie–Tooth disease 2a (hereditary motor and sensory neuropathy type IIA) (AD, 605995) | KIF1B | CSCA | – | + | – | One Japanese family described with the onset of symptoms in childhood |
| Hereditary spastic paraplegia, SPG10 (AD, 604187) | KIF5A | CSCA | – | + | – | Onset of symptoms at 8–40 years of age |
| Hereditary spastic paraplegia, SPG4 (AD, 182601) | SPG4 (SPASTIN) | CSCA | – | + | – | Gait disturbance due to degeneration of the corticospinal tract with onset at 20–39 years, mild cognitive impairment |
| Troyer syndrome, SPG20 (AR, 275900) | SPG20 (SPARTIN) | CSCA | – | + | – | Hereditary spastic paraplegia, dysarthria, distal amyotrophy, mild developmental delay, short stature; onset in early childhood |
| Spinocerebellar ataxia 5 (AD, 604985) | Beta-III spectrin | CSCA | – | + | – | Cerebellar cortex atrophy and purkinje cell loss; onset of disease 10–68 years of age |
| Lowe oculocerebrorenal syndrome (OCRL) (XL, 309300) | OCRL1 | CSCA | – | + | – | Bilateral congenital cataracts, mental retardation and renal Fanconi syndrome Variable life expectancy |
| Developmental malformations, deafness, and dystonia (AD, 607371). | Beta-Actin | CSCA | – | + | – | Developmental midline malformations, sensory hearing loss, and delayed-onset generalised dystonia syndrome |
| Sensorineural deafness: 1) AD, 607841 and AR, 601478 2) AD, 606346 and AR, 607821 3) AR, 600316) | 1) MYO1A, 2)MYO6, 3)MYO15A | CSCA | – | + | – | Non-syndromic sensorineural deafness |
| 1) Usher syndrome type IB (AR, 276900) | MYO7A (Myosin 7) | CSCA | – | + | + | Usher syndrome phenotype includes profound congenital deafness, vestibular areflexia, progressive retinitis pigmentosa, leading to blindness |
| 2) Sensorineural deafness (AD, 601317 and AR, 600060) | ||||||
| (1) Slow progressing amyotrophic lateral sclerosis (ALS8) (AD, 608627); (2) ALS typical, rapidly progressive (AD, 105400); (3) Late-onset spinal muscular atrophy (AD, 182980) | VAPB | VTF | – | + | – | Affected patients may have different presentations of motor neuron disease; clinical features are family-specific |
| ARC syndrome (AR, 208085) | VPS33B | VTF | – | + | + | Congenital abnormalities include arthrogryposis, hypotonia, renal fanconi syndrome, cholestatic jaundice, absence of platelet α granules, prolonged bleeding, recurrent infections, death in infancy |
| CEDNIK syndrome (AR, 609528) | SNAP29 | VTF | – | + | – | Cerebral dysgenesis, neuropathy, ichthyosis and keratoderma; also microcephaly, sensorineural deafness, optic disc hypoplasia, facial dysmorphism, intracranial abnormalities; death <4 months of age |
| Familial haemophagocytic lymphohistiocytosis (AR, 608898) | MUNC13-4 (UNC13D, HPLH3) | VTF | – | – | + | Infantile-onset activation of T lymphocytes: fever, pancytopenia, coagulopathy, liver failure |
| Familial haemophagocytic lymphohistiocytosis (AR, 603552) | SYNTAXIN 11 | VTF | – | + | + | As above, also severe psychomotor retardation |
| Limb girdle muscular dystrophy (AR, 253601); Miyoshi myopathy (AR, 254130) | DYSFERLIN | VTF | – | – | – | Limb girdle myopathy and/or distal myopathy; onset 12–39 years of age |