Identification through exome sequencing of the first PMM2-CDG individual of Mexican mestizo origin

González-Domínguez, Carlos; Raya-Trigueros, A.; Manrique-Hernández, S.; Jaimes, Alex; Salinas-Marín, Roberta; Molina-Garay, Carolina; Carrillo‐Sánchez, Karol; Flores-Lagunes, Luis Leonardo; Jiménez-Olivares, M.; Dehesa-Caballero, C.; Aláez-Verson, Carmen; Martínez-Duncker, Iván

doi:10.1016/j.ymgmr.2020.100637

Cited by 5 publications

(2 citation statements)

References 19 publications

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“…In most disease-related genes, variants affecting splicing are not fully characterized because variant screening is restricted to gDNA. In our experience involving ATP6V0A2-CDG and more recently PMM2-CDG, amplification of cDNA transcripts is an invaluable tool to demonstrate non-functional alternative splicing, identifying the consequence on the protein and establishing the pathogenicity mechanism ( Bahena-Bahena et al, 2014 ; González-Domínguez et al, 2020 , 2021 ). Of the six reported disease-causing mutations in HGMD that potentially affect splicing of ALG1 , only one has been experimentally confirmed ( Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele

et al. 2021

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This study reports on a Mexican mestizo patient with a multi-systemic syndrome including neurological involvement and a type I serum transferrin profile. Clinical exome sequencing revealed complex alleles in ALG1, the encoding gene for the chitobiosyldiphosphodolichol beta-mannosyltransferase that participates in the formation of the dolichol-pyrophosphate-GlcNAc2Man5, a lipid-linked glycan intermediate during N-glycan synthesis. The identified complex alleles were NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 208 + 25G > T] and NM_019109.5(ALG1): c.[208 + 16_208 + 19dup; 1312C > T]. Although both alleles carried the benign variant c.208 + 16_208 + 19dup, one allele carried a known ALG1 pathogenic variant (c.1312C > T), while the other carried a new uncharacterized variant (c.208 + 25G > T) causing non-functional alternative splicing that, in conjunction with the benign variant, defines the pathogenic protein effect (p.N70S_S71ins9). The presence in the patient’s serum of the pathognomonic N-linked mannose-deprived tetrasaccharide marker for ALG1-CDG (Neu5Acα2,6Galβ1,4-GlcNAcβ1,4GlcNAc) further supported this diagnosis. This is the first report of an ALG1-CDG patient from Latin America.

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Section: Discussionmentioning

confidence: 99%

ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele

et al. 2021

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“…PMM2 -CDG is not thoroughly diagnosed, since the phenotypes are similar to CP. Therefore, clinical awareness and molecular diagnosis should be performed to screen couples with infertility or miscarriage issues 21 and they should be appropriately counseled on the potential risk before subsequent pregnancies. In conclusion, we describe the first South Indian patient with autosomal recessive CDG-Ia with PMM2 c.710 C > T, T237M mutation inherited from carrier parents in accordance with the PMM2 -CDG type Ia.…”

Section: Discussionmentioning

confidence: 99%

PMM2-CDG T237M Mutation in a Patient with Cerebral Palsy-Like Phenotypes Reported from South India

Sreedevi,

Swapna,

Maruthy

et al. 2023

Glob Med Genet

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Congenital disorder of glycosylation (CDG) is an autosomal recessively inherited disorder. Hypotonia, stroke-like episodes, and peripheral neuropathy are also associated with the condition that typically develops during infancy. The patient, a 12-year-old girl born to healthy consanguineous parents, was diagnosed with cerebral palsy as a child. The affected patient has hypotonia, inadequate speech, strabismus, and developmental delay with mild mental retardation, which are key symptoms of CDG. Whole-exome sequencing (WES) identified the known missense pathogenic variant PMM2 c.710 C > T, p.T237M in the patient coding for the phosphomannomutase 2 (PMM2) confirming molecular testing of CDG. The patient's parents carried heterozygous PMM2 c.710 C > T variants. This study highlights the importance of WES in patients with a developmental disability or other neurological conditions, which is also useful in screening risk factors in couples with infertility or miscarriage issues.

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Characterization of a missense variant in COG5 in a Tunisian patient with COG5-CDG syndrome and insights into the effect of non-synonymous variants on COG5 protein

Khabou,

Sahari,

ben Issa

et al. 2024

J Hum Genet

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Identification through exome sequencing of the first PMM2-CDG individual of Mexican mestizo origin

Cited by 5 publications

References 19 publications

ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele

ALG1-CDG Caused by Non-functional Alternative Splicing Involving a Novel Pathogenic Complex Allele

PMM2-CDG T237M Mutation in a Patient with Cerebral Palsy-Like Phenotypes Reported from South India

Characterization of a missense variant in COG5 in a Tunisian patient with COG5-CDG syndrome and insights into the effect of non-synonymous variants on COG5 protein

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