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European Journal of Medical Genetics May 2020Congenital microcoria (MCOR) is an eye anomaly characterized by a pupil with diameter below 2 mm, and is caused by underdevelopment or absence of the dilator muscle of...
Congenital microcoria (MCOR) is an eye anomaly characterized by a pupil with diameter below 2 mm, and is caused by underdevelopment or absence of the dilator muscle of the pupil. Two types have been described: a recessive, syndromic (Pierson syndrome OMIM 609049) and a dominant, isolated form (MCOR syndrome OMIM 156600). Fares-Taie and colleagues described inherited microdeletions in chromosome band 13q32.1 segregating with dominant microcoria in several families. The GPR180 gene is located within the smallest commonly deleted region and encodes a G protein-coupled receptor involved in smooth muscle cells growth. We here describe a patient with isolated, non-syndromic MCOR. The patient presented with a blue iris and small pupils, non-reactive to cycloplegic agents. Her mother had a milder ocular phenotype, namely a blue iris with hypoplastic crypts and mild myopia. We present a detailed clinical examination and follow up. DNA from the index patient was analyzed for the presence of chromosomal imbalances using molecular karyotyping. The genetic test revealed a small duplication of chromosome band 13q32.1. The duplication affected a 289 kb region, encompassing 11 genes including GPR180. Interestingly, the patient displays only MCOR in contrast to patients with the reciprocal deletion who present with MCOR and iridocorneal angle dysgenesis. This genetic anomaly was inherited from the mother who carries the duplication in mosaic form, which should be considered when offering genetic counselling. In summary, we describe the first 13q32.1 duplication encompassing GPR180 associated with MCOR.
Topics: Adult; Child, Preschool; Chromosome Duplication; Chromosomes, Human, Pair 13; Eye; Female; Humans; Mosaicism; Pedigree; Pupil Disorders; Receptors, G-Protein-Coupled
PubMed: 32200002
DOI: 10.1016/j.ejmg.2020.103918 -
BMC Nephrology Jul 2017Congenital nephrotic syndrome (CNS) is a rare disorder caused by various structural and developmental defects of glomeruli. It occurs typically as an isolated kidney...
BACKGROUND
Congenital nephrotic syndrome (CNS) is a rare disorder caused by various structural and developmental defects of glomeruli. It occurs typically as an isolated kidney disorder but associates sometimes with other systemic, extrarenal manifestations.
CASE PRESENTATIONS
An infant presented with severe CNS, which progressed rapidly to renal failure at age of 3 months and death at 27 months. The clinical phenotypes and genetic causes were studied, including the renal pathology at autopsy. Besides the CNS, the affected child had remarkable right-side predominant eye-ball hypoplasia with bilateral anterior chamber dysgenesis (microcoria). Brain MRI revealed grossly normal development in the cerebrum, cerebellum, and brain stem. Auditory brainstem responses were bilaterally blunted, suggesting a defective auditory system. At autopsy, both kidneys were mildly atrophied with persistent fetal lobulation. Microscopic examination showed a diffuse global sclerosis. However, despite of the smaller size of glomeruli, the nephron number remained similar to that of the age-matched control. Whole-exome sequencing revealed that the affected child was compound heterozygous for novel truncating LAMB2 mutations: a 4-bp insertion (p.Gly1693Alafs*8) and a splicing donor-site substitution (c.1225 + 1G > A), presumably deleting the coiled-coil domains that form the laminin 5-2-1 heterotrimer complex.
CONCLUSIONS
Our case represents a variation of Pierson syndrome that accompanies CNS with unilateral ocular hypoplasia. The average number but smaller glomeruli could reflect either mal-development or glomerulosclerosis. Heterogeneous clinical expression of LAMB2 defects may associate with the difference in fetal β1 subtype compensation among affected tissues. Further study is necessary to evaluate incidence and features of auditory defect under LAMB2 deficiency.
Topics: Fatal Outcome; Female; Humans; Infant; Laminin; Loss of Function Mutation; Nephrons; Nephrotic Syndrome; Pedigree
PubMed: 28683731
DOI: 10.1186/s12882-017-0632-4 -
Anales de Pediatria (Barcelona, Spain :... Dec 2016
Topics: Abnormalities, Multiple; Eye Abnormalities; Female; Humans; Infant, Newborn; Mutation; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Pupil Disorders
PubMed: 26975222
DOI: 10.1016/j.anpedi.2016.01.025 -
BMJ Case Reports Jul 2020
Topics: Fatal Outcome; Humans; Infant, Newborn; Kidney Diseases, Cystic; Male; Myasthenic Syndromes, Congenital; Nephrotic Syndrome; Pupil Disorders
PubMed: 32616536
DOI: 10.1136/bcr-2020-236517