Clinical aspects of the MASA syndrome in a large family, including expressing females

Kaepernick, L; Legius, Eric; Higgins, James V.; Kapur, Saroj

doi:10.1111/j.1399-0004.1994.tb04019.x

Cited by 49 publications

(10 citation statements)

References 29 publications

(32 reference statements)

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“…Symptomatic female heterozygotes have been described for both AVPR2 and L1CAM mutations. The X-chromosome with the normal allele was found to be preferentially inactivated by methylation in the women with the disease phenotype [Kaepernick et al, 1994;Nomura et al, 1997;Kinoshita et al, 2004]. To our knowledge, the present patient is the only person described with a deletion of both L1CAM and AVPR2 with part of the ARHGAP4 gene.…”

Section: Discussionmentioning

confidence: 69%

Nephrogenic diabetes insipidus in a patient with L1 syndrome: A new report of a contiguous gene deletion syndrome including L1CAM and AVPR2

Knops

Bos

Kerstjens-Frederikse

et al. 2008

American J of Med Genetics Pt A

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We report on an infant boy with congenital hydrocephalus due to L1 syndrome and polyuria due to diabetes insipidus. We initially believed his excessive urine loss was from central diabetes insipidus and that the cerebral malformation caused a secondary insufficient pituitary vasopressin release. However, he failed to respond to treatment with a vasopressin analogue, which pointed to nephrogenic diabetes insipidus (NDI). L1 syndrome and X-linked NDI are distinct clinical disorders caused by mutations in the L1CAM and AVPR2 genes, respectively, located in adjacent positions in Xq28. In this boy we found a deletion of 61,577 basepairs encompassing the entire L1CAM and AVPR2 genes and extending into intron 7 of the ARHGAP4 gene. To our knowledge this is the first description of a patient with a deletion of these three genes. He is the second patient to be described with L1 syndrome and NDI. During follow-up he manifested complications from the hydrocephalus and NDI including global developmental delay and growth failure with low IGF-1 and hypothyroidism.

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Section: Discussionmentioning

confidence: 69%

Nephrogenic diabetes insipidus in a patient with L1 syndrome: A new report of a contiguous gene deletion syndrome including L1CAM and AVPR2

Knops

Bos

Kerstjens-Frederikse

et al. 2008

American J of Med Genetics Pt A

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“…Owing to the random inactivation of genes on the X chromosome, female carriers of L1 mutations are heterozygous at the level of the L1-expressing cells, in that each cell expresses either the normal or the mutated gene. In humans, heterozygous carriers (L1+/−) of the L1 syndrome usually show a mild phenotype, being thus very different from the severe symptoms of L1-deficient (L1-/y) males [13]. And in mice, contrary to what one would expect, heterozygous females show a complex set of morphological features that are not intermediate between wild-type (L1+/+) and fully L1-deficient (L1-/y) mice [14].…”

Section: Introductionmentioning

confidence: 82%

Heterozygous L1-deficient mice express an autism-like phenotype

Sauce

Wass

Netrakanti

et al. 2015

Behavioural Brain Research

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“…However, variable expressivity has been observed, even within families, with the most severe cases resulting in prenatal death and other cases presenting with mild ventricular enlargement compatible with long‐term survival [Finckh et al, ]. Female carriers of L1CAM mutations are typically asymptomatic; however, they may present with adducted thumbs, intellectual disability, or varying degrees of hydrocephalus [Kaepernick et al, ].…”

Section: Introductionmentioning

confidence: 99%

L1CAM whole gene deletion in a child with L1 syndrome

Chidsey

Baldwin

Toydemir

et al. 2014

American J of Med Genetics Pt A

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L1 syndrome is a group of overlapping, X-linked disorders caused by mutations in L1CAM. Clinical phenotypes within L1 syndrome include X-linked hydrocephalus with stenosis of the aqueduct of sylvius (HSAS); mental retardation, adducted thumbs, shuffling gait, and aphasia (MASA) syndrome; spastic paraplegia type 1; and agenesis of the corpus callosum. Over 200 mutations in L1CAM have been reported; however, only a few large gene deletions have been observed. We report on a 4-month-old male with a de novo whole gene deletion of L1CAM presenting with congenital hydrocephalus, aqueductal stenosis, and adducted thumbs. Initial failure of L1CAM gene sequencing suggested the possibility of a whole gene deletion of L1CAM. Further investigation through chromosome microarray analysis showed a 62Kb deletion encompassing the first exon of the PDZD4 gene and the entire L1CAM gene. Investigations into genotype-phenotype correlations have suggested that mutations leading to truncated or absent L1 protein cause more severe forms of L1 syndrome. Based on the presentation of the proband and other reported patients with whole gene deletions, we provide further evidence that L1CAM whole gene deletions result in L1 syndrome with a severe phenotype, deletions of PDZD4 do not cause additional manifestations, and that X-linked nephrogenic diabetes insipidus reported in a subset of patients with large L1CAM deletions results from the loss of AVPR2.

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Clinical aspects of the MASA syndrome in a large family, including expressing females

Cited by 49 publications

References 29 publications

Nephrogenic diabetes insipidus in a patient with L1 syndrome: A new report of a contiguous gene deletion syndrome including L1CAM and AVPR2

Nephrogenic diabetes insipidus in a patient with L1 syndrome: A new report of a contiguous gene deletion syndrome including L1CAM and AVPR2

Heterozygous L1-deficient mice express an autism-like phenotype

L1CAM whole gene deletion in a child with L1 syndrome

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