Exome sequencing reveals a novel homozygous mutation in ACP33 gene in the first Italian family with SPG21

Scarlato, Marina; Citterio, Andrea; Barbieri, Anna Maria; Godi, Claudia; Panzeri, Elena; Bassi, Maria Teresa

doi:10.1007/s00415-017-8558-0

Cited by 4 publications

(8 citation statements)

References 9 publications

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“…Neither of the variants reported in this study represent a frequent polymorphism according to the Genome Aggregation Database ( 9 ). Apart from the abovementioned families I and II, all reported families outside the Amish community harbor different mutations ( 4 , 7 , 8 ): the reported four European families with SPG21 (Austria, Germany, and Italy) ( 3 , 8 ) all show truncating mutations like those in the Amish families ( 4 , 8 ). The Asian family, however, displayed missense mutations ( 7 ).…”

Section: Discussionmentioning

confidence: 96%

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Mast Syndrome Outside the Amish Community: SPG21 in Europe

et al. 2022

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Background:Mast syndrome is a rare disorder belonging to the group of hereditary spastic paraplegias (HSPs). It is caused by bi-allelic mutations in the ACP33 gene, and is originally described in Old Order Amish. Outside this population, only one Japanese and one Italian family have been reported. Herein, we describe five subjects from the first three SPG21 families of German and Austrian descent.Methods:Five subjects with complicated HSP were referred to our centers. The workup consisted of neurological examination, neurophysiological and neuropsychological assessments, MRI, and genetic testing.Results:Onset varied from child- to adulthood. All patients exhibited predominant spastic para- or tetraparesis with positive pyramidal signs, pronounced cognitive impairment, ataxia, and extrapyramidal signs. Neurophysiological workup showed abnormal motor and sensory evoked potentials in all the patients. Sensorimotor axonal neuropathy was present in one patient. Imaging exhibited thin corpus callosum and global brain atrophy. Genetic testing revealed one heterozygous compound and two homozygous mutations in the ACP33 gene.Conclusion:Herein, we report the first three Austrian and two German patients with SPG21, presenting a detailed description of their clinical phenotype and disease course. Our report adds to the knowledge of this extremely rare disorder, and highlights that SPG21 must also be considered in the differential diagnosis of complicated HSP outside the Amish community.

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Section: Discussionmentioning

confidence: 96%

“…Mast syndrome was first described in the Old Order Amish population ( 6 ). Outside the Amish population, one Japanese case and one Italian family have been reported ( 3 , 7 , 8 ). We report the first three families with Mast syndrome in German- speaking countries.…”

Section: Introductionmentioning

confidence: 99%

Mast Syndrome Outside the Amish Community: SPG21 in Europe

et al. 2022

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“…3,4 The common clinical features of ABHD21and ABHD16Arelated disorders are motor developmental delay, pyramidal and extrapyramidal signs, thin corpus callosum, and white-matter hyperintensity on MRI. [6][7][8][9] The nonsense variant was predicted to be pathogenic by MutationTaster (https://www.mutationtaster.org/). The variant identified in our patients had not been registered in gnomAD (https:// gnomad.broadinstitute.org/), Human Genetic Variation Database, 10 ABHD16A encodes "abhydrolase domain containing 16A, phospholipase (ABHD16A)," which has lipase activity that converts phosphatidylserine to lysophosphatidylserine.…”

Section: Genetic Analysismentioning

confidence: 99%

A homozygous ABHD16A variant causes a complex hereditary spastic paraplegia with developmental delay, absent speech, and characteristic face

Miyake

Silva²,

Troncoso

et al. 2021

Clinical Genetics

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Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous genetic disease characterized by progressive weakness and spasticity predominantly affecting the lower limbs. Complex HSP is a subset of HSP presenting with additional neuronal and/or non-neuronal phenotypes. Here, we identify a homozygous ABHD16A nonsense variant in two affected children in a Chilean family. Very recently, two groups reported patients with biallelic ABHD16A whose clinical presentation was similar to that of our patients. By reviewing the clinical features of these reports and our patients, ABHD16A-related HSP can be characterized by early childhood onset, developmental delay, intellectual disability, speech disturbance, extrapyramidal signs, psychiatric features, no sphincter control, skeletal involvement, thin corpus callosum, and high-intensity signals in white matter on T2-weighted brain MRI. In addition, our affected siblings showed a characteristic face, sleep disturbance, and nodular and hyperpigmented skin lesions, which have not previously been reported in this condition.

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“…Among these reported variants, two variants producing frameshifts (p. Arg40Glufs*27 and p. Thr201Asnfs*13) cause generally identical symptoms. 1 , 3 However, the Japanese patients carrying the homozygous missense variant (p. Ala108Pro), which was next to the critical site of the alpha/beta hydrolase fold domain (Ser109), showed strikingly late‐onset HSP symptoms without bulbar, extrapyramidal, or cerebellar signs. 2 The large deletion in SPG21 have not been reported before.…”

Section: Figurementioning

confidence: 99%