CLOUSTON SYNDROME: FIRST CASE IN RUSSIA Marakhonov AV, Skoblov MYu, Galkina VA, Zinchenko RA *Corresponding Author: Andrey V. Marakhonov, Scientifi c Associale Laboratory of Genetic Epidemiology,
Federal State Budgetary Institution “Research Centre for Medical Genetics” under The Russian Academy
of Medical Sciences, Moskvorechie St., 1, 115478 Moscow, Russian Federation; Tel./Fax: +7(499)612-80-
45; E-mail: marakhonov@generesearch.ru page: 51
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MATERIALS AND METHODS
A blood sample was obtained during standard
genetic counseling at the Laboratory of Genetic
Epidemiology of the Research Centre for Medical
Genetics, Russian Academy of Medical Science,
Moscow, Russian Federation. The study was approved
by its Internal Review Board (IRB).
DNA was isolated with the salting out procedure
[9]. The polymerase chain reaction (PCR)
mixtures contained 50 pg of the template, 1 nM each of the forward and reverse primers, 2.5 mM
MgCl2, 0.2 mM dNTP mix, 0.5 units of Taq DNA
polymerase, and 1 ´ Taq buffer in a total volume
of 10 ml. All samples were denatured for 1 min.
at 94°C, followed by 35 cycles of denaturation at
94°C for 10 seconds, annealing at 62°C for 5 seconds,
and extension at 72°C for 90 seconds in a
Tercyc thermocycler (DNA-Technology, Moscow,
Russia). Oligonucleotides were synthesized by
Lytech Inc., Moscow, Russian Federation (http://
www.lytech.ru); forward: 5’-TGT AAT ATC ACC
GTG TCA CTT-3’ and reverse: 5’-CAA ACT CTT
CAG GCT ACA GAA-3’. Bidirectional sequencing
of PCR fragments was performed according
to the fl uo-rescence-tagged chain termination protocol
(BigDye Terminator; Applied Biosystems,
Carlsbad, CA, USA) followed by fractionation on
an ABI PRISM™ 310 automated DNA sequencer
(Applied Biosystems).
A 28-year-old Russian woman was referred to
the Research Centre for Medical Genetics, Moscow,
Russian Federation in June 2007, because of alopecia,
palmoplantar hyperkeratosis and nail dystrophy
(Figure 1). She mentioned that she had the above
symptoms from early childhood. Moreover, she
noted that her mother and maternal grandfather had
the same problem since their birth. During clinical
examination it was diagnosed as hypohidrotic ectodermal
dysplasia, alopecia (with very sparse hair
on her scalp, length about 15-20 cm, no eyelashes,
eyebrows, axillary and pubic hair), clubbing of the
fi ngers and palmar hyperkeratosis with dystrophy
and hypoplasty of the nails, progressive corneal
dystrophy (with photophobia and conjunctivitis).
The patient showed normal teeth and intellectual
development. Light microscopy of hair on the scalp revealed thin hair, smooth hair shaft with absence
of structural defects in the examined sample. The
patient was worried about the risk of having an affected
child.
During genetic counseling, Clouston syndrome
was hypothesized and the woman was sent for molecular
genetic screening of mutations in the GJB6
gene. We performed whole gene sequencing using
primers fl anking the open reading frame of the
gene, which revealed a heterozygous non synonymous
substitution c.263C>T (Figure 2, upper chromatogram).
At the protein level, the mutation leads
to the amino acid substitution p.A88V. This is one
of the mutations found in patients with HED2.
In-depth analysis of the pedigree of the
proband’family revealed that at least one person in
each generation was affected (Figure 3). This information
supported the autosomal dominant type of
disease inheritance. Unfortunately, all other affected
relatives were dead so we were unable to perform
medical and molecular genetic analyses on them.
Nevertheless, the patient decided to have a child.
The 32-year-old husband of the proband was normal.
Thus, the risk of the birth of an affected child
was 50% in this case. The pregnancy was unremarkable.
During prenatal screening of chorionic villi,
the child was determined to have a normal genotype
of the GJB6 gene (Figure 2, lower chromatogram).
The child’s parameters at birth were within the normal range.
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