New autosomal recessive chondrodysplasia???pseudohermaphrodism syndrome

Nivelon, A; Nivelon, J L; Mabille, J P; Maroteaux, P; Feldman, Jeremy; Douvier, S.; Aymé, Ségolène

doi:10.1097/00019605-199210000-00005

Cited by 14 publications

(25 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, none of the bone dysplasias associated with developmental delay has shown the clinical and radiological features identical to those of our patients, including Dyggve-Melchior-Clausen dysplasia [Beighton, 1990], spondyloepimetaphyseal dysplasia with joint laxity [Beighton and Kozlowski, 1980], spondyloepiphyseal dysplasia tarda with mental retardation described by Kohn et al [1984], familial spondyloepiphyseal dysplasia tarda with characteristic facies reported by Huson et al [1993], and chondrodysplasia with pseudohermaphrodism described by Nivelon et al [1992].…”

Section: Discussionsupporting

confidence: 66%

Previously undescribed spondyloepiphyseal dysplasia associated with craniosynostosis, cataracts, cleft palate, and mental retardation: Report of four sibs

et al. 1998

View full text Add to dashboard Cite

We report on four Japanese sibs (three brothers and one sister) with a previously unreported syndrome of spondyloepiphyseal dysplasia, craniosynostosis, cataracts, cleft palate, and mental retardation. Most clinical manifestations were evident neonatally, but skeletal changes and cataracts became substantial in early childhood. Radiological anomalies comprised coronal synostosis, mild epiphyseal dysplasia, particularly in the distal tibiae, strikingly delayed patellar ossification, mild metaphyseal splaying, hypoplastic ilia with iliac flare, and platyspondyly with ovoid-shaped or posteriorly humped vertebral bodies. The nonconsanguineous parents were mildly mentally retarded, and sibs of both gender were equally affected; thus, inheritance was likely autosomal recessive.

show abstract

Section: Discussionsupporting

confidence: 66%

Previously undescribed spondyloepiphyseal dysplasia associated with craniosynostosis, cataracts, cleft palate, and mental retardation: Report of four sibs

et al. 1998

View full text Add to dashboard Cite

show abstract

“…The second sibling had a 46,XX karyotype with histologically normal ovaries, but otherwise exhibited similar phenotypic abnormalities including severe dwarfism and generalized chondrodysplasia [29]. Pregnancy was interrupted after ultrasound examination at 17 weeks of gestation.…”

Section: Resultsmentioning

confidence: 99%

Loss of Function Mutation in the Palmitoyl-Transferase HHAT Leads to Syndromic 46,XY Disorder of Sex Development by Impeding Hedgehog Protein Palmitoylation and Signaling

et al. 2014

View full text Add to dashboard Cite

The Hedgehog (Hh) family of secreted proteins act as morphogens to control embryonic patterning and development in a variety of organ systems. Post-translational covalent attachment of cholesterol and palmitate to Hh proteins are critical for multimerization and long range signaling potency. However, the biological impact of lipid modifications on Hh ligand distribution and signal reception in humans remains unclear. In the present study, we report a unique case of autosomal recessive syndromic 46,XY Disorder of Sex Development (DSD) with testicular dysgenesis and chondrodysplasia resulting from a homozygous G287V missense mutation in the hedgehog acyl-transferase (HHAT) gene. This mutation occurred in the conserved membrane bound O-acyltransferase (MBOAT) domain and experimentally disrupted the ability of HHAT to palmitoylate Hh proteins such as DHH and SHH. Consistent with the patient phenotype, HHAT was found to be expressed in the somatic cells of both XX and XY gonads at the time of sex determination, and Hhat loss of function in mice recapitulates most of the testicular, skeletal, neuronal and growth defects observed in humans. In the developing testis, HHAT is not required for Sertoli cell commitment but plays a role in proper testis cord formation and the differentiation of fetal Leydig cells. Altogether, these results shed new light on the mechanisms of action of Hh proteins. Furthermore, they provide the first clinical evidence of the essential role played by lipid modification of Hh proteins in human testicular organogenesis and embryonic development.

show abstract

“…We identified the second homozygous missense variant c.770T>C, p. (Leu257Pro) in HHAT as a disease causing variation in two sisters with microcephaly and cerebellar vermis hypoplasia. Callier et al () described the first homozygous variant (p. Gly287Val) of HHAT underlying the diagnosis of Nivelon–Nivelon–Mabille syndrome (MIM 600092) of the only described family in the literature (Nivelon et al, ; Thauvin‐Robinet et al, ). In their original and follow up papers, authors described two female siblings with a unique phenotype displaying generalized chondrodysplasia, intrauterine and postnatal growth retardation, microcephaly with cerebellar vermis hypoplasia and facial dysmorphism.…”

Section: Discussionmentioning

confidence: 99%

“…In their original and follow up papers, authors described two female siblings with a unique phenotype displaying generalized chondrodysplasia, intrauterine and postnatal growth retardation, microcephaly with cerebellar vermis hypoplasia and facial dysmorphism. Unexpectedly, one of the female sibs had 46, XY gonadal dysgenesis (Nivelon et al, ; Thauvin‐Robinet et al, ). Although, our patients did not show dwarfism, generalized chondrodysplasia and micromelia like those described as Nivelon–Nivelon–Mabille syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, it is still possible that our patients represent the mild form of the syndrome but the incomplete knowledge and the rarity of cases may account in part for confusion. Thus, additional reports will help in better delineation of this very rare and unique autosomal recessive condition (Callier et al, ; Nivelon et al, ; Thauvin‐Robinet et al, ). The Nivelon–Nivelon–Mabille syndrome was proposed to be a result of a loss of function in the HHAT gene (Callier et al, ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Biallelic novel missense HHAT variant causes syndromic microcephaly and cerebellar‐vermis hypoplasia

Abdel-Salam

Mazen

Eid

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

We report two siblings with microcephaly, early infantile onset seizures, and cerebellar vermis hypoplasia, in whom whole exome sequencing revealed a novel homozygous missense (c.770T>C, p.[Leu257Pro]) variant in the hedgehog acyl‐transferase gene (HHAT), encoding an enzyme required for the attachment of palmitoyl residues that are critical for multimerization and long and short range hedgehog signaling. There is a report of one family with Nivelon–Nivelon–Mabille syndrome in which HHAT was proposed as the likely candidate gene. The phenotypic overlap with the family we report herein provides further evidence implicating HHAT in cerebellar development and the pathogenesis of this rare spectrum.

show abstract

New autosomal recessive chondrodysplasia???pseudohermaphrodism syndrome

Cited by 14 publications

References 0 publications

Previously undescribed spondyloepiphyseal dysplasia associated with craniosynostosis, cataracts, cleft palate, and mental retardation: Report of four sibs

Previously undescribed spondyloepiphyseal dysplasia associated with craniosynostosis, cataracts, cleft palate, and mental retardation: Report of four sibs

Loss of Function Mutation in the Palmitoyl-Transferase HHAT Leads to Syndromic 46,XY Disorder of Sex Development by Impeding Hedgehog Protein Palmitoylation and Signaling

Biallelic novel missense HHAT variant causes syndromic microcephaly and cerebellar‐vermis hypoplasia

Contact Info

Product

Resources

About