Compound heterozygous variants in PGAP1 causing severe psychomotor retardation, brain atrophy, recurrent apneas and delayed myelination: a case report and literature review

Hypomyelinating leukodystrophies (HL) is a group of genetically heterogeneous neurodegenerative disorders characterized by a lack of brain myelin deposition. One of the most common autosomal recessive HL is HL type 7 caused by mutations in the POLR3A gene. We reported the first clinical case of a Russian patient with HL type 7.Proband is a 7‑year‑old patient with HL type 7. The diagnosis was confirmed by genealogy, neurological examination, brain magnetic resonance imaging and molecular genetic testing. Two compound‑heterozygous variants in the POLR3A gene were revealed in the patient. Each variant was described earlier in patients with variable clinical manifestations of neurodegenerative diseases. The peculiarities of clinical manifestations in our patient were the manifestation of the disease in the first year of life, the predominance of cerebellar symptoms, a movement limitation of the jaw, leading to worsening of dysarthria, a delay in the formation of permanent teeth and short stature. The course of the disease was moderate that could be explained by different effect of the variants in the POLR3A gene.POLR3A‑related disease is a group of clinically heterogeneous disorders manifesting from early childhood to adulthood and characterized by isolated spastic ataxia or ataxia combined with oligodontia and hypogonadotropic hypogonadism, isolated or complicated spastic paraplegia, as well as a combination of ataxia with extrapyramidal symptoms. Our case report demonstrates the complexity of diagnostic process in the absence of a peculiar clinical picture and specific changes in brain imaging.

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A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review

Neurogenetics ◽

10.1007/s10048-021-00682-1 ◽

2022 ◽

Author(s):

Salvatore Iacono ◽

Elda Del Giudice ◽

Alberta Leon ◽

Vincenzo La Bella ◽

Rossella Spataro

Keyword(s):

Case Report ◽

Literature Review ◽

Krabbe Disease ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Adult Onset ◽

Disease Case

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PRUNE Syndrome Is a New Neurodevelopmental Disorder

Child Neurology Open ◽

10.1177/2329048x17752237 ◽

2018 ◽

Vol 5 ◽

pp. 2329048X1775223 ◽

Cited By ~ 5

Author(s):

Majid Alfadhel ◽

Marwan Nashabat ◽

Khalid Hundallah ◽

Amal Al Hashem ◽

Ahmed Alrumayyan ◽

...

Keyword(s):

Corpus Callosum ◽

Developmental Delay ◽

Brain Atrophy ◽

Neurodevelopmental Disorder ◽

Brain Magnetic Resonance Imaging ◽

Compound Heterozygous Mutation ◽

Compound Heterozygous ◽

Neurodevelopmental Disease ◽

Dysmorphic Features ◽

Delayed Myelination

PRUNE syndrome, or neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (OMIM#617481), is a new rare autosomal recessive neurodevelopmental disease that is caused by homozygous or compound heterozygous mutation in PRUNE1 on chromosome 1q21. Here, We report on 12-month-old and 30-month-old girls from 2 unrelated Saudi families with typical presentations of PRUNE syndrome. Both patients had severe developmental delay, progressive microcephaly, and dysmorphic features. Brain magnetic resonance imaging showed slight thinning in the corpus callosum, mild frontal brain atrophy, and delayed myelination in one of the patients. Both patients had the same missense mutation in PRUNE1 (c.383G>A, p.Arg128Gln), which was not reported before in a homozygous state. We compared our patients to previously reported cases. In conclusion, We suggest that clinicians consider PRUNE syndrome in any child presenting with dysmorphic features, developmental delay, progressive microcephaly, central hypotonia, peripheral spasticity, delayed myelination, brain atrophy, and a thin corpus callosum.

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