Dataset Information

Mucopolysaccharidosis type I due to maternal uniparental disomy of chromosome 4 with partial isodisomy of 4p16.3p15.2.

ABSTRACT: Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disease caused by biallelic mutations in IDUA, the gene coding for the lysosomal enzyme alpha L-iduronidase. Clinically MPS I is a chronic progressive multisystem disease typically presenting with coarse facial features, skeletal deformities, joint contractures, and multi-organ involvement. Hurler syndrome (MPS IH) represents the severe end of the spectrum of mucopolysaccharidosis type I and is characterized by central nervous system involvement leading to childhood dementia. Here we report on a severe affected MPS IH patient who is homozygous for a splice site mutation (c.158 + 1G > A) in the IDUA gene. Further analyses revealed maternal uniparental disomy of chromosome 4 with partial isodisomy of the telomeric end of chromosome 4 (4.p16.3p15.2), representing an extraordinary mode of inheritance with a much lower re-occurrence risk for MPS I in the family.

SUBMITTER: Katja K

PROVIDER: S-EPMC7582098 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Mucopolysaccharidosis type I due to maternal uniparental disomy of chromosome 4 with partial isodisomy of 4p16.3p15.2.

Katja Kloth K Inga Vater V Ramona Lindschau L Almuth Caliebe C Maria Muschol Nicole MN

Molecular genetics and metabolism reports 20201022

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disease caused by biallelic mutations in <i>IDUA</i>, the gene coding for the lysosomal enzyme alpha <i>L-</i>iduronidase. Clinically MPS I is a chronic progressive multisystem disease typically presenting with coarse facial features, skeletal deformities, joint contractures, and multi-organ involvement. Hurler syndrome (MPS IH) represents the severe end of the spectrum of mucopolysaccharidosis type I and is characterized by centra ...[more]

PMID: 33117653

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Project description:Background:Uniparental disomy (UPD) is a rare condition in which a child inherits both copies of a chromosome or chromosome segment from one parent. Medical consequences of UPD may include abnormal imprinting, unmasking of genetic disease, and somatic mosaicism; alternatively, the condition may be clinically silent. We present a case of maternal UPD for chromosome 6, a rare condition previously reported less than 20 times. In our patient with a normal phenotype, the condition was discovered through abnormal paternity testing results. Uniparental isodisomy is a rare cause of discordant parentage testing results, but it is an important phenomenon to recognize. Case presentation:We present a female born at 32?weeks gestational age with birth weight 10-25%ile when corrected for prematurity. Paternity testing was obtained for legal reasons, and initial results appeared to exclude the alleged father. However, the lab performed additional testing which indicated that the patient was homozygous for maternal alleles for all three tested loci located on chromosome 6. Based on these results, the patient was referred for a medical genetics evaluation for possible maternal uniparental disomy. She presented for her consultation at 10?months of age and appeared to be developing appropriately. Her age-adjusted weight, length, and head circumference were <3%ile, 10%ile, and 25%ile respectively. Chromosomal microarray testing confirmed maternal UPD6. The patient was seen again at 14?months of age, and her weight and length were 10-25%ile. She had not developed concerning symptoms or physical exam findings. Conclusions:The presence of UPD, especially in asymptomatic patients, has implications for paternity testing, as standard methods may miss cases of both isodisomy and heterodisomy. This rare inheritance pattern should be considered when discordant paternity results come under suspicion. It is unusual for a parentage testing lab to perform the amount of testing done for this case, but the initial inconsistencies necessitated further investigation. UPD6 has uncertain effects and variable phenotypes, so this patient's genetic abnormality likely would have gone undiscovered if not for the non-medical indication for the laboratory analysis. Her asymptomatic presentation raises the possibility that UPD may be more common than previously estimated.

Dataset Information

Mucopolysaccharidosis type I due to maternal uniparental disomy of chromosome 4 with partial isodisomy of 4p16.3p15.2.

Publications

Mucopolysaccharidosis type I due to maternal uniparental disomy of chromosome 4 with partial isodisomy of 4p16.3p15.2.

Similar Datasets

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