Lily Bello

Mrs. Betts
Biology 6
February 6, 2014
Nail Patella Syndrome
Nail patella syndrome, Fong disease, urner!"ieser syndrome, and #sterrei$%er
syndrome. %ese are all names &or t%e geneti$ disorder t%at is most $ommonly 'no(n as
Nail Patella Syndrome )NPS*, (%i$% (as dis$o+ered in 1,46, by -r. .. Fong. Fong
dis$o+ered t%is disease (%en %e (as resear$%ing %ig% blood pressure and albuminuria in
a pregnant (oman. S%e s%o(ed t%e symptoms o& nail patella syndrome, (%i$% %ad ne+er
been seen be&ore )2). %is disorder is $aused by a mutation in t%e gene LM/1B, (%i$%
$an be &ound on $%romosome ,. %e $%an$e o& %a+ing nail patella syndrome is about 1
out o& e+ery 00,000 )6*. 1lt%oug% t%is disorder is not &atal, it $an still $ause pain and
problems &or people diagnosed.
%ere are multiple symptoms &ound in people (%o %a+e nail patella syndrome.
%e most $ommon symptoms are to %a+e nails (it% dents and s%apes in t%em, and
abnormal &eatures in t%e 'nees. %ese symptoms are t%e reason (%y t%is disease is o&ten
$alled 2nail patella syndrome3, be$ause it usually se+erely a&&e$ts t%e nails and t%e patella
)also 'no(n as t%e 'nee$ap* o& t%e patient. #t%er $ommon symptoms in$lude an
e4tremely %ig% %airline, early!de+eloped glau$oma, and a $%an$e o& %a+ing 'idney
disease as li&e progresses. Most o& t%e symptoms 'no(n to NPS are &airly $ommon to
t%e disorder, and are used to diagnose, sin$e t%ey are &ound in almost all patients. But, not
all symptoms are so easy to noti$e and so $ommon. 5lia$ %orns, &or e4ample, are a
symptom t%at is not &ound in all patients, and $an be identi&ied as a bump on t%e pel+i$
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bone o& some people (%o %a+e t%is disorder )6*.
1lmost e+eryone (%o %as NPS (ill %a+e di&&erent t%an a+erage nails.
Possibilities are dented nails, nails (it% triangular $oloring in t%em, bro'en nails, or e+en
t%e la$' o& a $omplete nail. %e nail t%at is a&&e$ted most is t%e t%umbnail, and least is
t%e pin'y nail. Nail abnormalities su$% as t%ese $an be used to diagnose NPS, be$ause
t%is symptom is so $ommon to t%is disease. 1lso, patients (ill typi$ally %a+e somet%ing
(rong (it% t%eir 'nee. %e patella $ould be eit%er s%aped in a (ay t%at it is not supposed
to be or missing &rom t%e 'nee in general. 5n t%e $ase (%ere t%e 'nee$ap is miss%aped, it
(ould be easy &or t%e 'nee$ap to be dislo$ated. %is $ould $ause pain to t%e patient, or
$ause t%e patient to be unstable )6*. 1lt%oug% %a+ing a +ery %ig% %airline is a symptom
o& NPS, it doesn7t $ause a patient any pain and $an 8ust be ignored. 9lau$oma is (%en
t%ere is pressure in t%e eye, and $an $ause blindness i& it7s not properly treated. Being
diagnosed earlier t%an most people is a symptom o& NPS. 1lso, early 'idney disease is a
symptom o& NPS, and $an be dangerous to t%e patient as (ell.
Nail patella syndrome is tested &or in many (ays. 1s stated by n$bi.go+, it $ould
be tested &or by $ytogeneti$ tests su$% as F5S:!metap%ase testing, or by one o& t%e types
o& mole$ular geneti$s tests )se;uen$e analysis o& t%e entire $oding region, targeted +ariant
analysis, deletion<dupli$ation analysis, or se;uen$e analysis o& sele$t e4ons* )0*.
=ytogeneti$ testing, one (ay t%at people are tested &or NPS, is (%en t%e number and
stru$ture o& t%e $%romosomes are 2analy>ed3, &or problems t%at $ould o$$ur or are going
to o$$ur sometime in t%e &uture )?*. %is type o& testing $an ta'e a long time to be
$omplete t%oug%, up to 2 (ee's. Mole$ular geneti$ testing is (%en t%e -N1 is
in+estigated, &or a spe$i&i$ se;uen$e o& genes t%at $ould mean diseases. 5n simpli&ied
(ords, t%is is done by ta'ing nu$lei$ a$id, ma'ing $opies, and t%en adding dye and
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loo'ing &or t%e se;uen$es t%at are $%anged )1*.
%is disorder %as many met%ods t%at are used to relie+e patients o& t%e symptoms
t%at $ome (it% nail patella syndrome. Sin$e all o& t%e symptoms are so di&&erent, ea$%
symptom t%at is e4perien$ed is treated di&&erently. For e4ample, (%en patients (it% NPS
%a+e issues in+ol+ing t%eir bones or 8oints, surgery $ould be a possibility &or t%em. But,
&or people (%o 8ust %a+e 'nee problems be$ause o& NPS, less in+ol+ed treatment su$% as
a 'nee bra$e or t%erapy may be a better option )6*. 1lso, sin$e people (it% nail patella
syndrome are at a greater ris' o& 'idney disease and glau$oma, t%ey s%ould begin
s$reenings &or t%ese diseases at an early age and $ontinue t%em t%roug%out t%eir li&e. %is
(ill %elp in early diagnosis o& t%ese diseases, and %ope&ully more e&&e$ti+e treatment.
Nail patella syndrome %as no li&e e4pe$tan$y be$ause it is not &atal. 1lt%oug%
many geneti$ disorders are &atal (%en t%e patient is %omo>ygous, it %as not been pro+en
&or nail patella syndrome ),*. Sin$e people (it% nail patella syndrome %a+e a %ig%er
$%an$e o& de+eloping 'idney disease, t%is $ould a&&e$t t%e amount o& years t%ey li+e. But,
t%e ot%er symptoms do not %a+e an e&&e$t o& t%e li&e span o& someone (it% NPS, no
matter %o( mu$% o& an annoyan$e t%ey may $ause to patients (%o e4perien$e t%em.
Nail patella syndrome is an autosomal dominant disease. %is means t%at i& one
parent is %omo>ygous dominant &or t%e gene, t%en t%e $%ild produ$ed (ill %a+e NPS. 1s
long as t%e dominant gene is present in t%e $%ild7s $%romosome, t%ey (ill de&initely %a+e
nail patella syndrome. %is is a gene mutation, be$ause it a&&e$ts t%e gene 2LM/1B3 on
$%romosome ,. 5t does not a&&e$t t%e entire $%romosome@ it 8ust mutates t%e one gene.
%e Punnett S;uare s%o(n in 2Figure 13 s%o(s
t%e situation (%en one parent %as nail patella syndrome
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!Figure 1!
and one does not. %e purple bo4es signi&y t%e possibilities t%at (ould %a+e nail patella
syndrome and t%e blue bo4es s%o( t%e possibilities t%at (ould not %a+e nail patella
syndrome. Sin$e t%is disease is an autosomal dominant disease, any instan$e (%ere an
indi+idual $arries t%e dominant gene means t%at t%ey (ill %a+e t%e disease. 5n t%is
punnett s;uare, one parent is %omo>ygous re$essi+e. %is parent does not %a+e nail
patella syndrome. %e ot%er parent is %etero>ygous, (%i$% means t%at t%ey do %a+e nail
patella syndrome, but t%ere is t%e possibility t%at t%ey $ould pass on t%e re$essi+e gene to
t%eir $%ild. Figure 1 s%o(s t%at i& a %etero>ygous parent and a %omo>ygous re$essi+e
parent %a+e $%ildren, t%at t%e $%ild (ould %a+e a 00A $%an$e o& %a+ing NPS and a 00A
$%an$e o& not %a+ing NPS.
%e gene t%at is a&&e$ted by t%is disease is t%e LM/1B gene, (%i$% $an be &ound
on $%romosome ,. %e LM/1B gene is part o& t%e gene &amily $alled %omeobo4es. %is
means t%at all t%e genes t%at are %omeobo4es s%are $ommon $%ara$teristi$s. %e spe$i&i$
$%ara$teristi$ t%at %omeobo4es s%are is t%at t%ey all 2dire$t t%e &ormation o& many body
stru$tures during early embryoni$ de+elopment3 )4*. 1ll %omeobo4es also %a+e a same
-N1 se;uen$e t%at gi+es $ells dire$tions to ma'e a spe$i&i$ strand o& amino a$ids, $alled
t%e %omeodomain. Most proteins t%at %a+e %omeodomain in t%em are trans$ription
&a$tors, (%i$% is (%at t%e LM/1B gene is supposed to produ$e. %e normal &un$tion o&
t%is gene is to gi+e instru$tions to $reate a protein $alled t%e 2trans$ription &a$tor3. %is
protein t%en atta$%es to spe$i&i$ pla$es on -N1, and also %elps to regulate (%at %appens
in ot%er genes. 1s said on 9eneti$s%omere&eren$e.$om, 2%e protein appears to be
parti$ularly important during early embryoni$ de+elopment o& t%e limbs, 'idneys, and
eyes3 )4*. %is statement ma'es $omplete sense, be$ause t%is is (%at t%e normal &un$tion
o& a %omeobo4 (ould be in+ol+ed in.
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%e stru$ture o& t%e mutated gene $an be di&&erent &rom t%e regular gene in many
(ays. 1s it (as said on geneti$s%omere&eren$e.$om, 21t least 140 mutations in
t%e LMX1B gene %a+e been &ound to $ause nail!patella syndrome3 )4*. But, alt%oug%
t%ere are lots o& di&&erent mutations, t%e ma8ority o& t%em end up $reating a +ersion o& t%e
protein t%at is s%orter t%an t%e normal protein, and does not do (%at it is meant to. 1side
&rom t%is, it $ould also $%ange one amino a$id in t%e gene. .it%er (ay, 2a mutation in t%e
LM/1B gene $reates nail patella syndrome, alt%oug% resear$%ers are not sure (%y3 )4*.
ypi$ally, t%e mutation t%at o$$urs in nail patella syndrome is eit%er a deletion or an
in+ersion. B%en one amino a$id is s(it$%ed (it% anot%er, t%at (ould $ause t%e &un$tion
o& t%e gene to not (or' $orre$tly and (ould end up $ausing nail patella syndrome. 1s
stated by 9eneti$s :ome Ce&eren$e, 2-eletions o& t%e entire LM/1B gene or large
portions o& t%e gene %a+e also been s%o(n to $ause nail patella syndrome3 )4*.
%e &un$tion o& t%e gene is a&&e$ted by t%e $%ange in stru$ture be$ause sin$e t%e
amino a$id se;uen$e in t%e gene is di&&erent t%an usual, it gi+es instru$tions to ma'e a
protein t%at is di&&erent t%an normal. %ese instru$tions $ause t%e &un$tion to $%ange by
%a+ing t%e gene ma'e t%e (rong protein, and t%is ne( protein $annot (or' t%e (ay t%at it
s%ould. %ere is no e4planation &or t%e reasons o& t%e symptoms, as stated in t%e ;uote
abo+e &rom sour$e 4.
5n $on$lusion, nail patella syndrome is a geneti$ disorder t%at a&&e$ts t%e
nails and 'nees, (it% t%e possibility o& ot%er symptoms. 1lt%oug% it is not &atal, it $an be
sin$e it $an $ause 'idney disease. 1lt%oug% it does not %a+e a $ure, people (ill nail
patella (ill most li'ely %a+e a long, %appy li&e t%an's to modern day treatments and
s$reenings &or t%e symptoms.
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Bor's =ited
1: "ie$%le, Frederi$' L., M.-., P%. -. DB%at 5s Mole$ular -iagnosti$sED Go Molecular.
1bbott Mole$ular, n.d. Beb. 21 Feb. 2014. F%ttpG<<(((.gomole$ular.$om<dis$o+er<
(%atHisHmole$ularHdiagnosti$s.%tmlI.
2: "ni&&in, =assandra L. DNail Patella Syndrome.D Omim. Jo%n :op'ins Kni+ersity, n.d.
Beb. 6 Feb. 2014. F%ttpG<<omim.org<entry<161200Esear$%LnailA20patella
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A20syndromeM%ig%lig%tL'nee$apA20patellarA20syndromeA20syndromi$A20patella
A20nailA20'neepanI.
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