A novel phenotype associated with cutis laxa, abnormal fat distribution, cardiomyopathy and cataract

Asbeck, Ellyze van; Wolthuis, David F.G.J.; Mohamed, Miski; Wevers, Ron A.; Korenke, Cristoph G.; Gardeitchik, Thatjana; Morava, Éva

doi:10.1002/ajmg.a.36392

Cited by 5 publications

(12 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, novel metabolic CL syndromes were added to the growing list of ARCL. Their clinical presentation highly overlaps with the phenotypic spectrum of ARCL2A [6,7] and ARCL2B [8]. Mutations in ATP6V1A (MIM 617403) and ATP6V1E1 (MIM 617402), two components of the V-ATPase complex, were shown to cause ARCL2A, and a very similar phenotype to that seen in ATP6V0A2-CDG [7].…”

mentioning

confidence: 97%

Expanding the phenotype of metabolic cutis laxa with an additional disorder of N-linked protein glycosylation

Witters

Breckpot²,

Foulquier

et al. 2017

Eur J Hum Genet

Self Cite

View full text Add to dashboard Cite

Genetic syndromes associated with cutis laxa (CL) and wrinkled skin are multisystem disorders with progeroid features, including sagging, lax and wrinkled skin [1, 2]. Metabolic CL is genetically heterogeneous. We previously reported on the frequently overlapping clinical phenotypes, including X-linked and autosomal recessive forms [2]. However, recently new forms of CL have been described. "Metabolic" CL is related to different inborn errors of metabolism; the historic example is the X-linked defect in ATP7A (MIM 309400). Autosomal recessive metabolic CL types are ARCL2 and ARCL3. ARCL2 patients present with a characteristic face, skeletal and joint abnormalities, developmental and growth delay due to mutations in different genes, including ATP6V0A2 (MIM 219200, 278250), RIN2 (MIM 613075), COG7(MIM 608779), GORAB (MIM 231070), and PYCR1 (MIM 612940, 614438) [2-4]. These encode endosomal and Golgi proteins (ARCL2A), and affect trafficking and glycosylation, except for PYCR1, which is involved in mitochondrial proline synthesis (ARCL2B). ARCL3 patients have parchment-like, progeroid skin, cataracts, corneal clouding, and significant neurologic disease [5], caused by mutations in PYCR1 or ALDH18A1 (MIM 616603, 219150), also involved in mitochondrial proline synthesis [2]. Additional inborn

show abstract

mentioning

confidence: 97%

Expanding the phenotype of metabolic cutis laxa with an additional disorder of N-linked protein glycosylation

Witters

Breckpot²,

Foulquier

et al. 2017

Eur J Hum Genet

Self Cite

View full text Add to dashboard Cite

show abstract

“…These affected individuals also show strong cutis laxa with redundant skin at birth. The facial appearance is similar to ARCL2C affected individuals 1,17 . Some affected individuals present with cardiac abnormalities and seizures 1 .…”

Section: Introductionmentioning

confidence: 64%

Expanding the clinical and molecular spectrum of ATP6V1A related metabolic cutis laxa

Vogt

Choubassi

Herczegfalvi

et al. 2021

J of Inher Metab Disea

View full text Add to dashboard Cite

Several inborn errors of metabolism show cutis laxa as a highly recognizable feature. One group of these metabolic cutis laxa conditions is autosomal recessive cutis laxa type 2 caused by defects in v-ATPase components or the mitochondrial proline cycle. Besides cutis laxa, muscular hypotonia and cardiac abnormalities are hallmarks of autosomal recessive cutis laxa type 2D (ARCL2D) due to pathogenic variants in ATP6V1A encoding subunit A of the v-ATPase. Here, we report on three affected individuals from two families with ARCL2D in whom we performed whole exome and Sanger sequencing. We

show abstract

“…Supplementary Material 1 | Gene structure of AGK and localization of identified mutations (1)(2)(3)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Red font indicates newly reported mutations.…”

Section: Data Availability Statementmentioning

confidence: 99%

“…The AGK gene is located on chromosome 7q34 and consists of 16 exons (1). To date, several studies have identified different types of loss-of-function mutations in the AGK gene, including start codon mutations, nonsense, frameshift, and splice site mutations (1)(2)(3)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). AGK is a mitochondrial protein that catalyzes the phosphorylation of diacylglycerol (DAG) and monoacylglycerol (MAG) to phosphatidic acid (PA) and lysophosphatidic acid (LPA), respectively.…”

Section: Introductionmentioning

confidence: 99%

Case Report: Two Chinese Infants of Sengers Syndrome Caused by Mutations in AGK Gene

Wang

Shan

et al. 2021

Front. Pediatr.

View full text Add to dashboard Cite

Sengers syndrome (OMIM #212350) is a rare autosomal recessive disorder due to mutations in acylglycerol kinase (AGK) gene. We report two cases that were diagnosed clinically and confirmed genetically. Both infants had typical clinical features characterized by hypertrophic cardiomyopathy, bilateral cataracts, myopathy, and lactic acidosis, and heart failure was the most severe manifestation. Genetic testing of a boy revealed a homozygous pathogenic variant for Sengers syndrome in AGK (c.1131+2T>C) which was classified as likely pathogenic according to the ACMG guideline; besides, his skeletal muscle biopsy and transmission electron microscope presented obvious abnormity. One girl had compound heterozygous (c.409C>T and c.390G>A) variants of AGK gene that was identified in the proband and further Sanger sequencing indicated that the parents carried a single heterozygous mutation each. After the administration of “cocktail” therapy including coenzyme Q10, carnitine, and vitamin B complex, as well as ACEI, heart failure and myopathy of the boy were significantly improved and the condition was stable after 1-year follow-up, while the cardiomyopathy of the girl is not progressive but the plasma lactate acid increased significantly. We present the first report of two infants with Sengers syndrome diagnosed via exome sequencing in China.

show abstract

A novel phenotype associated with cutis laxa, abnormal fat distribution, cardiomyopathy and cataract

Cited by 5 publications

References 18 publications

Expanding the phenotype of metabolic cutis laxa with an additional disorder of N-linked protein glycosylation

Expanding the phenotype of metabolic cutis laxa with an additional disorder of N-linked protein glycosylation

Expanding the clinical and molecular spectrum of ATP6V1A related metabolic cutis laxa

Case Report: Two Chinese Infants of Sengers Syndrome Caused by Mutations in AGK Gene

Contact Info

Product

Resources

About