New CDH3 mutation in the first Spanish case of hypotrichosis with juvenile macular dystrophy, a case report
Blanco-Kelly et al. BMC Medical Genetics
New CDH3 mutation in the first Spanish case of hypotrichosis with juvenile macular dystrophy, a case report
Fiona Blanco-Kelly 0 1 3 4
Luciana Rodrigues-Jacy da Silva 1 4
Iker Sanchez-Navarro 1 4
Rosa Riveiro-Alvarez 0 1 3 4
Miguel Angel Lopez-Martinez 1 4
Marta Corton 0 1 3 4
Carmen Ayuso 0 1 2 3 4
0 Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto Carlos IIII (ISCIII) , Madrid , Spain
1 Department of Medical Genetics, Instituto de Investigación Sanitaria - Fundación Jiménez Díaz, (IIS-FJD, UAM) , Madrid , Spain
2 Department of Genomics and Genetics, Fundación Jiménez Díaz University Hospital , Av. Reyes Católicos n° 2, 28040 Madrid , Spain
3 Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Instituto Carlos IIII (ISCIII) , Madrid , Spain
4 Department of Medical Genetics, Instituto de Investigación Sanitaria - Fundación Jiménez Díaz, (IIS-FJD, UAM) , Madrid , Spain
Background: CDH3 on 16q22.1 is responsible for two rare autosomal recessive disorders with hypotrichosis and progressive macular dystrophy: Hypotrichosis with Juvenile Macular Dystrophy and Ectodermal Dysplasia, Ectrodactyly and Macular Dystrophy. We present a new case of Hypotrichosis with Juvenile Macular Dystrophy. Case presentation: A Spanish male born in 1998 from non-consanguineous healthy parents with a suspected diagnosis of Keratosis Follicularis Spinulosa Decalvans and Retinitis Pigmentosa Inversa referred to our Genetics Department (IIS-Fundación Jiménez Díaz). Molecular study of ABCA4 was performed, and a heterozygous missense p.Val2050Leu variant in ABCA4 was found. Clinical revision reclassified this patient as Hypotrichosis with Juvenile Macular Dystrophy. Therefore, further CDH3 sequencing was performed showing a novel maternal missense change p.Val205Met (probably pathogenic by in silico analysis), and a previously reported paternal frameshift c.830del;p.Gly277Alafs*20, thus supporting the clinical diagnosis.. Conclusions: This is not only the first Spanish case with this clinical and molecular diagnosis, but a new mutation has been described in CDH3. Moreover, this work reflects the importance of joint assessment of clinical signs and evaluation of pedigree for a correct genetic study approach and diagnostic.
Macular dystrophy; CDH3; Hypotrichosis; Syndromic retinal dystrophy; Case report
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Background
The CDH3 gene, on16q22.1, encodes for P-cadherin,
which is expressed in retina epithelial cells and in hair
follicles, being responsible for adherens junctions
(calcium dependent cell-cell adhesion molecule) in these
and other epithelial tissues [1, 2]. Additionally, CDH3 is
thought to be a marker of the epithelial tissues
progenitor cells and it has been found to be expressed in human
embryonic stem cells [3, 4].
This gene is responsible for two rare autosomal
recessive disorders: Hypotrichosis with Juvenile Macular
Dystrophy (HJMD, OMIM: 601553) [5–17] and Ectodermal
Dysplasia, Ectrodactyly and Macular Dystrophy (EEM,
OMIM: 225280) [18]. Both disorders characterized by
hypotrichosis and progressive retinal dystrophy.
To date, according to Orphanet (http://www.orpha.net,
date of access 11/05/2016) the frequencies of HJMD and
EEM are unknown and across the world only 50 cases of
HJMD and approximately 15 cases of EEM (only three
with molecular characterization) [8, 19] have been
described.
HJMD has been described as macular degeneration
and short sparse scalp hair from birth with hair loss
during the first months of life [5]. The retinal phenotype is
nowadays being re-evaluated. It has been suggested that
earlier onset is more likely than the juvenile stated on its
name [7, 20–22], and that there is a wider involvement
of the retina (not only the macula) [7, 20–23]. Thus,
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defining the retinal alteration as a more complex retinal
dystrophy rather than a solely macular dystrophy.
The hair can present different types of abnormalities
being pili-torti one of the most frequent (twisted hair
shafts on the long axis, which are brittle, and break at
varying lengths with many areas appearing bald) [5, 24].
It usually affects the scalp but can also affect eyebrows
and eyelashes (body hair is normal) [5, 24].
Patients with EEM syndrome, additionally exhibit a
wider range of features such as split hand/foot
malforma (...truncated)