Autosomal recessive agammaglobulinemic patient with a novel large deletion in IGHM presenting with mild clinical phenotype

Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

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Identification of a Large Deletion, Spanning Exons 4 to 11 of the Human Factor XIIIA Gene, in a Factor XIII-Deficient Family

Blood ◽

10.1182/blood.v91.1.149.149_149_153 ◽

1998 ◽

Vol 91 (1) ◽

pp. 149-153 ◽

Cited By ~ 1

Author(s):

Rashida Anwar ◽

Krzysztof J.A. Miloszewski ◽

Alexander F. Markham

Keyword(s):

Autosomal Recessive ◽

Molecular Genetic ◽

Point Mutations ◽

Autosomal Recessive Disorder ◽

Large Deletion ◽

Factor Xiiia ◽

Paternal Allele ◽

Bleeding Tendency ◽

Genetic Studies ◽

Polymerase Chain

Inherited deficiency of factor XIIIA subunit (FXIIIA) is an autosomal recessive disorder that is characterized by a life-long bleeding tendency and complications in wound healing. Molecular genetic studies have shown the deficiency can be due to small sequence changes within the FXIIIA gene, such as point mutations or microdeletions. On molecular analysis of the FXIIIA gene in an FXIII-deficient patient, of United Kingdom origin, we identified a putative homozygous missense mutation, Arg408Gln. However, the father of this patient is homozygous normal for arginine at codon 408. Having proved paternity in this pedigree by microsatellite analysis, we examined the FXIIIA RNA of the patient by reverse transcriptase-polymerase chain reaction and found the paternal allele to lack exons 4 through 11 inclusive. Hence, a huge deletion extending from intron 3 to intron 11 and the Arg408Gln mutation are jointly responsible for FXIIIA deficiency in this family. This is the first finding of such a large deletion in the FXIIIA gene.

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Single amino acid loss in the dystrophin protein associated with a mild clinical phenotype

Muscle & Nerve ◽

10.1002/mus.25190 ◽

2016 ◽

Vol 55 (1) ◽

pp. 46-50 ◽

Cited By ~ 2

Author(s):

Roser Pons ◽

Kyriaki Kekou ◽

Artemis Gkika ◽

George Papadimas ◽

Nikolaos Vogiatzakis ◽

...

Keyword(s):

Amino Acid ◽

Clinical Phenotype ◽

Single Amino Acid ◽

Dystrophin Protein ◽

Mild Clinical Phenotype

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GPT2 mutations in autosomal recessive developmental disability: extending the clinical phenotype and population prevalence estimates

Human Genetics ◽

10.1007/s00439-019-02057-x ◽

2019 ◽

Vol 138 (10) ◽

pp. 1183-1200

Author(s):

Qing Ouyang ◽

Brian C. Kavanaugh ◽

Lena Joesch-Cohen ◽

Bethany Dubois ◽

Qing Wu ◽

...

Keyword(s):

Developmental Disability ◽

Autosomal Recessive ◽

Clinical Phenotype ◽

Population Prevalence ◽

Prevalence Estimates

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SYNE1-related autosomal recessive cerebellar ataxia, congenital cerebellar hypoplasia, and cognitive impairment

Clinics and Practice ◽

10.4081/cp.2018.1071 ◽

2018 ◽

Cited By ~ 1

Author(s):

Lauren Swan ◽

John Cardinal ◽

David Coman

Keyword(s):

Cognitive Impairment ◽

Autosomal Recessive ◽

Age Of Onset ◽

Clinical Phenotype ◽

Cerebellar Hypoplasia ◽

Childhood Onset ◽

Spectrin Repeat ◽

Disease Phenotypes ◽

Related Disease ◽

Autosomal Recessive Cerebellar Ataxia

The spectrin repeat-containing nuclear envelope protein 1 (SYNE1) gene encodes a family of spectrin structural proteins that are associated with anchoring the plasma membrane to the actin cytoskeleton. SYNE1-related disease is most commonly reported in autosomal recessive spinocerebellar ataxia 8, which demonstrates variable age of onset with a median of 30 years of age. However pathogenic mutations in SYNE1 are also causative of arthrogryposis multiplex congenital, a severe congenital neuromuscular condition. Here in we report monozygous twins with childhood onset ataxia, cerebellar hypoplasia, dysarthria, and cognitive impairment sharing two novel heterozygous mutations in the SYNE1 gene. Our family may expand the clinical phenotype associated with SYNE1-related disease and offers possible genotype-phenotype correlations of a rare continuum of clinical disease phenotypes from neonatal to adult onset.

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